OCULAR MANIFESTATIONS OF HIV/AIDS AT MOI

TEACHING REFERAL HOSPITAL    

(AMPATH CLINIC)

 

 

A dissertation submitted in part fulfilment for the degree of masters of Medicine

(Ophthalmology) at the University of Nairobi

 

 

 

 

 

 

DR. NGONA BANGA LISTO

 

 

YEAR 2008

 

 

 

 

 

DECLARATION

 

 

This dissertation is my original work and has not been presented for a degree at any other university.

 

 

 

 

 

 

 

 

 

Signed----------------------------------                                       Date------------------------------

 

Dr. Listo Ngona Banga

 

APPROVAL

 

This dissertation has been submitted in part fulfilment of the degree of masters of medicine in ophthalmology with our approval as university supervisors.

 

Signed_______________________                           Date____________________

 

Dr. K.H.M. Kollmann (FEACO)

MBChB (Goettingen), MD (Goettingen), DTMMP (Hamburg), M.Med. Opthalmol. (Munich), MBA Health Care Management (Durban)

Senior Lecturer, Department of Ophthalmology, University of Nairobi

Signed________________________                         Date___________________

 

Dr. K. Kimani

MBChB (U.O.N), M.Med.Opthalmol. (U.O.N), MSC CEH (UCL, London)

Lecturer, Department of Ophthalmology, University of Nairobi

Signed_______________________                            Date_______________________

 

Dr. C. Owino

MBChB (U.O.N), M.Med. Opthalmol. (U.O.N)

Lecturer, Department of Ophthalmology, Moi University

Signed___________________________                   Date_________________________

DEDICATION

 

This dissertation is dedicated to my darling Mami Grace, our beloved daughters Benita, Atali, Abigail and Eunice.

 

 

 

 

 

 

 

 

 

 

 

 


ACKNOWLEDGEMENTS

 

I am grateful to my supervisors, Dr. KHM Kollmann and Dr. K Kimani, and Dr. C Owino, for their invaluable assistance and healthy critique, without which this study would not be what it is.

Many thanks to the administrations of Moi Teaching Referral Hospital, AMPATH clinic, for allowing this study to be carried out in their institutions and for giving all the necessary assistance.

Special thanks to all my lecturers in the department of ophthalmology for their invaluable support towards my study in ophthalmology. I also thank the consultants at KNH, all support staff at the department and KNH and my colleagues. I also wish to thank CBM for their support.

 

 

 

 

 

 

 

 

 

 

 

 

 

 


TABLE OF CONTENTS

                                                                                                                                                Page No.

DECLARATION.. ii

APPROVAL.. iii

DEDICATION.. iii

ACKNOWLEDGEMENTS. iii

TABLE OF CONTENTS. iii

LIST OF TABLES. iii

LIST OF FIGURES. iii

LIST OF ABREVIATIONS. iii

ABSTRACT.. iii

1.0. INTRODUCTION.. 3

1. 1  Statement of the Problem of HIV/AIDS. 3

1.2    Background Information. 3

1.2.2  Diagnosis and Treatment 3

1.2.3  CD4+ T-Lymphocyte Count as a Predictor of Risk. 3

1.3  Moi Teaching Referral Hospital (MTRH). 3

2.0. LITERATURE REVIEW... 3

2.1  Prevalence and Pattern of Ophthalmic Manifestations. 3

2.2  Association between Ocular Manifestations and CD4. 3

3.0. OBJECTIVES. 3

3.1 Broad Objective: 3

3.2 Specific Objectives. 3

4.0. METHODOLOGY.. 3

4.1 Study Design: 3

4.2  Study Population: 3

4.3  Eligibility Criteria: 3

4.3.1  Inclusions Criteria: 3

4.3.2  Exclusion Criteria. 3

4.4  Sample Size. 3

4.5  Study Setting. 3

4.6  Study Period. 3

4.7  Data Collection. 3

4.8  Data Analysis. 3

4.10 Procedures. 3

4.11  Limitations. 3

4.12  Ethical Issues. 3

5.0. RESULT.. 3

6.0. DISCUSSION.. 3

7.0. CONCLUSIONS. 3

8.0. RECOMMENDATIONS. 3

9.0      REFERENCES. 3

10.0    APPENDICES

...... 10.1   Appendix 1: Qestionnaire. 3

...... 10.2   Appendix 2: Participants’ Concent Form.. 3

...... 10.3.   Appendix 3: WHO Classification of HIV/AIDS. 3

 

 


LIST OF TABLES

 

Table 1: CD4 + T -Lymphocyte Count in Patient Presenting with Common HIV Associated Disorders Involving the Eye. 3

Table 2: Baseline Data of the Study Patients. 3

Table 3: Ocular Examinations. 3

Table 4: ARV Treatment 3

Table 5: Association between Ocular Manifestation and CD4-Count 3

Table 6: Association between Ocular Manifestation and Systemic disease. 3

Table 7: Association between Adnexal Findings and current CD4 count 3

Table 8: Association between Posterior segment Findings and current CD4 count 3

Table 9: Association between Ocular Manifestation WHO staging and ARV Treatment 3

Table 10: Factors associated with presence of Ocular manifestations 3

 


LIST OF FIGURES

Figure 1: Viral cycle indicating the action points of drugs. 3

Figure 2: Distribution by Sex. 3

Figure 3: Distribution by Level of Education. 3

Figure 4: Distribution by Age. 3

Figure 5: WHO Visual Acuity Classification in Better Eye. 3

Figure 6: Prevalence of Ocular Manifestation among patients HIV/Aids 3

Figure 7: Pattern of Ocular Manifestation. 3

Figure 8: Adnexal Findings. 3

Figure 9: Anterior Segment Findings. 3

Figure 10: Posterior Segment Findings 3

Figure 11: Neurophthalmology Findings) 3

Figure 12: Systemic Manifestation. 3

Figure 13: Level of Current CD4 Count 3

Figure 14: HIV/AIDs per WHO Staging. 3

 


LIST OF ABREVIATIONS

 

AIDS              :           Acquired Immunodeficiency Syndrome

AMPATH       :           Academic Module for Prevention and Treatment of HIV/AIDS

ARVT             :           AntiRetroviral Therapy

CMV               :           Cytomegalovirus

ETB                 :           Extra-pulmonary tuberculosis

HAART          :           Highly Active antiretroviral therapy

HIV                 :           Human Immunodeficiency Virus

HZO               :           Herpes Zoster Ophthalmicus

HZ                   :           Herpes Zoster

MTRH             :           Moi Teaching Referral Hospital

NNRTI            :           Non-nucleoside Reverse Transcriptase inhibitors

NRTI               :           Nucleoside Reverse-transcriptase Inhibitors

WHO              :           World Health Organization                 

OPC                :           Oropharyngeal Candidiasis

TB                   :           Tuberculosis

KS                   :           Kaposi Sarcoma

PGL                 :           Peripheral Generalized Lymphadenopathy


ABSTRACT

 

AIM:  The management of patients with HIV/AIDS has improved in Kenya with the creation of comprehensive care units. This study was conducted to determine the pattern and prevalence of ocular manifestations in adolescents and adults with HIV/AIDS in order to contribute to the management of patients infected with HIV/AIDS.

METHODOLOGY:  This was a hospital based cross sectional study at Moi Teaching Referral Hospital (AMPATH CLINIC).  Adolescent and adult HIV/AIDS patients with or without symptoms/signs of AIDS attending the AMPATH clinic in MTRH (Eldoret) were randomly selected and after informed consent recruited into the study. At the eye clinic, detailed ocular examination was carried out and the findings recorded in a questionnaire and later analyzed using the SPSS version 12.0

RESULTS:  A total of 200 HIV/AIDS Patients were examined. The prevalence of ocular findings was 77%. The most common findings were observed in the posterior segment in 53% of the patients, followed by anterior segment in 26.5%. Retinal microvasculopathy (37.5%), chorioretinitis (4.5%), vitreous opacities (4%), macular edema (4%) and CMVretinitis (2.5%) were the main posterior segment findings. Fibrous membrane attached to the iris mostly near the papillary margin (18.5%) and iridocyclitis (5.5%) were the main anterior segment findings. Conjunctival growth (6.5%), Herpes zoster ophthalmicus (6.5%) and Kaposi (5%), conjunctival microvasculopathy (4%) and molluscum contagiosum (2.5%) were the main ocular adnexal findings. Tuberculosis was the main systemic finding (53%).

CONCLUSIONS: The prevalence of ocular finding in HIV/AIDS patients at MTRH was found to be high at 77%. Retinal microvasculopathy was the commonest retinal findings observed. Ocular findings were directly related to the severity of the clinical state of the disease (WHO clinical staging; p value 0.001) and to the severity of immune suppression (CD4+ count; p =0.044).


1.0       INTRODUCTION

The earliest known case of HIV was from a blood sample collected in 1959 from a man in Kinshasa, Democratic republic of Congo (1). Genetic analysis of this blood sample suggests that HIV-1 may have stemmed from a single virus in the late 1940 or early 1950. It is known that the virus has existed in the USA at least since the late 1970’s. From 1979-1981 rare types of pneumonia, cancer and others illnesses were being reported by doctors in Los Angeles and New York among a number of gay male patients (2). These were conditions not usually found in people with healthy immune systems and were attributed to immunosuppression.

The etiologic agent of AIDS is a retrovirus designated HIV, (Human Immunodeficiency Virus) (3). The CD4 T Lymphocyte is the primary target for HIV infections because of the affinity of the virus for the CD4 surface marker. The CD4 T Lymphocyte coordinates a number of important immunologic structures and loss of these, result in progressive impairment of the immune response. The CD4 T Lymphocyte counts are used to guide clinical and therapeutic management of HIV infected patients.

Since it was first described in 1981, Acquired Immunodeficiency Syndrome (AIDS) has become a major concern to all doctors, irrespective of their area of study or specialization. Ophthalmologists have not been spared. They are often called upon to make the initial diagnosis of AIDS, most often; however, they are requested to help treat the ocular manifestation of related opportunistic infection. These can have disastrous consequences for sight, especially for patient who are first seen when already markedly debilitated.

Practicing ophthalmologists are faced with the challenges to recognize and treat potentially sight threatening conditions and to identify unusual presentations.

1. 1.  Statement of the Problem of HIV/AIDS

The Human Immuno-deficiency Virus (HIV) infection has spread worldwide with various adverse health economic implications particularly in the developing world.

A global summary of the HIV/AIDS epidemic from December 2003 by joint United Nations Program for HIV/AIDS (UNAIDS) and WHO estimate that there are 40 million people worldwide living with HIV/AIDS (5).

At present about 90% of HIV infected persons live in developing countries in particular in sub-Sahara Africa and South East Asia.

The eye is affected in 50 -75% of adult patients (6). These observations indicate that regular screening of HIV positive patients is warranted to allow early identification of potential vision and life threatening disease  (7) .

1.2 Background Information

1.2.2 Diagnosis and Treatment

There are several ways of making a diagnosis of HIV/AIDS.

The HIV tests available for diagnosis include antibody testing such as Enzyme Immune Assay (home kits, rapid tests, saliva tests, urine tests, and vaginal secretion), Immunofluorescent Assay and Western Blot. The available antigen tests include P24 antigen and peripheral blood monocyte  Polymerase Chain Reaction (PBMC DNA PCR).

Plasma viral load can also be measured using the reverse transcriptase polymerase chain reaction method. This involves amplifying proviral DNA in the laboratory so that a diagnosis of infection can be made. It does not depend on antibodies but on the presence of the virus within the monocytes and allows diagnosis of infection in infant who still carry antibody passed from the HIV+ mother.

The viral life cycle is important when considering the drugs to combat HIV. New drugs under development target different parts of the life cycle. Reverse transcriptase is targeted by 3 classes of drugs; the NNRTI ( non nucleoside reverse transcriptase inhibitors), the NRTI ( nucleoside reverse transcriptase inhibitors) and the nucleotide RTI. Viral protease is targeted by protease inhibitors drugs such as ritonavir and Fusion is targeted by fusion inhibitors drugs such as enfuvirtide.

 

Figure 1: Viral cycle indicating the action points of drugs (3, 5)

 The detailed mode of action of the 3 classes of antiretroviral is as follows:

a.       Reverse transcriptase (RT) inhibitors (NRTI, NNRTI): inhibit reverse transcriptase (prevent copying of viral RNA to DNA, blocks subsequent steps in viral replication). The nucleoside (NRTI)/nucleotide analogues compete with natural substrate while non nucleoside inhibitors (NNRTI) bind at different site and change activity.

b.      Protease inhibitors (PI): inhibit the protease enzyme thereby preventing viral proteins from becoming functional. They mimic peptide bonds i.e. look like proteins to the protease enzyme and they compete with the natural substrate. 

c.       Fusion inhibitors: prevents fusion of viral envelope with the cell membrane and prevents entry of viral RNA and proteins into cell.

1.2.3 CD4+ T-Lymphocyte Count as a Predictor of Risk

CD4+ count in lymphocyte proved to be a reliable predictor of ocular complications in HIV infection (8).  The increased use of highly active antiretroviral therapy has allowed substantial and sustained, albeit incomplete, repopulation of T lymphocytes to occur in many patient. Such observations have raised the question  whether reconstituted T lymphocyte population are in fact functional and, more specially, whether the current or the lowest CD4 T lymphocyte count is a better predictor of the risk of HIV- associated disorders.

For years, the CD4+ T-lymphocyte count proved a reliable predictor of the risk of ocular complications of HIV infection (Table 1).  Recently, however, the use of highly active antiretroviral therapy (HAART), which consists of a combination of nucleoside reverse transcriptase inhibitors, HIV protease inhibitors and non nucleoside reverse transcriptase inhibitors, has decreased plasma levels of HIV RNA and increased CD4+ T lymphocyte counts, improving the immune function of patients with HIV infection (6). The clinical presentation of HIV related diseases may be modified by HAART, which has dramatically improved the prognosis of HIV infection. Before the introduction of HAART, patients with cytomegalovirus retinitis commonly had CD4+ counts less than 50 cells/µl, usually with minimal ocular inflammation (7). There are reports of spontaneous resolution of cytomegalovirus retinitis in patients with increased CD4+ counts related to such therapy, although the recovery in T lymphocyte may take months (9). Nevertheless, substantial intraocular inflammation in patients with healed cytomegalovirus retinitis receiving HAART has been reported, which is known as immune recovery uveitis (6).

Table 1: CD4 + T -Lymphocyte Count in Patients Presenting with Common HIV-Associated Disorders Involving the Eye (6,8)

CD4+ Count

Disorder

<500cells/mm3

 

 

 

<250 cells/mm3

 

 

<100cells/mm3

Kaposi’s sarcoma

Lymphoma

Tuberculosis

 

Pneumocystis carini

Toxoplasmosis

 

Retinal / Conjuctival microvasculopathy

Cytomegalovirus retinitis

Keratoconjuctivitis sicca

Varicella zoster virus retinitis

Mycobacterium avium complex infection

Cryptococcosis

Microsporidiosis

HIV encephalopathy      

Progressive multifocal leucoencephalopathy

 

 

1.3. Moi Teaching Referral Hospital (MTRH)

Moi Teaching and Referral Hospital (MTRH) is located in the Rift Valley Province of Kenya in Eldoret town. The MTRH has grown over the past 90 years from a native cottage hospital to a National Referral Hospital. It was started in 1917 as a cottage hospital that had a bed capacity of 60 to cater for African health needs. In 1978, the hospital was elevated and its staffing improved. The Eldoret District Hospital as it was known then, was serving as a referral hospital and provincial facility for other hospitals within Western Kenya. The bed capacity currently stands at 550.

The hospital has’ since grown to incorporate the Academic Model for the Prevention and Treatment of HIV/AIDS (AMPATH) which is a Kenya-USA partnership between Moi University School of Medicine, MTRH in Eldoret, in collaboration with USA Medical schools headed by Indiana School of Medicine. AMPATH has 18 comprehensive HIV/AIDS care clinics in urban and rural centres in Western Kenya. As of April 2007 it had enrolled over 45,317 patients, of these, 20,808 are on  ARVs.

The overriding goal of AMPATH is to establish a working model of both urban and rural comprehensive HIV preventive and treatment services, representing the unique attributes of academic institutions. AMPATH has structured its patients care programs to simultaneously provide HIV related teaching and research. The pilot phase of AMPATH began in November 2001. In  a bid to mount a meaningful response to the HIV pandemics, AMPATH has set up infrastructure and human resources capable of effectively managing the complex issues surrounding anti retroviral therapy and cost effective systems that ensure sustainable patients care and support. Established in November 2001, with funds born largely by private donations from the US and selected grant support, it has made significant progress and the last few years: established adult and paediatric HIV treatment services at Moi Teaching and Referral Hospital and other satellite hospitals and health centres like Mosoriot, Turbo, Burnst Forest, Amukura, Naitiri, Chulaimbo, Webuye, Kitale, Kapengura, Teso, Mt ELGON, Iten, Kabarnet, Busia and Port Victoria; trained medical staff in the provision of comprehensive multi dispensary care of HIV infected patient; demonstrated cost effective initial workup, treatment strategies and monitoring of HIV infected adults and children; developed a fully computerized medical record and data registry; established a fully functional  HIV reference laboratory capable of providing CD4-counts, viral load and PCR DNA testing.

It has been the goal of AMPATH to demonstrate working programs worthy of ongoing support by agencies, foundations and the Government of Kenya. It is at this clinic with it’s large patient turnover that this research was carried out. 


2.0       LITERATURE REVIEW

 

2.1              Prevalence and Pattern of Ophthalmic Manifestations

 

Numerous ophthalmic manifestations of HIV infection may involve the anterior or posterior segment of the eye. Since the first report of the ocular manifestations of AIDS by Holland et al. in 1982 (10), subsequent studies have described several AIDS related conditions in the eye and orbit.

2.1.1    Adnexal Manifestations

The ocular adnexal include the eyelids, conjunctiva, and lachrymal drainage system. In a review article by Cunningham et al the most common complications affecting these structures are herpes zoster, Kaposi’s sarcoma, Molluscum contagiosum, conjunctival growth and conjunctival microvasculopathy (8).

In Malawi, Lewallen et al noted that the commonest first presentations in HIV infected patients was herpes zoster ophthalmicus involving the lids (11).

In a study  by  Giorgis et al in Ethiopia, conjunctival  microvasculopathy (64% of them having CD4 less than 50) was by far the commonest accounting for 25/65 (38.1%), followed by Molluscum contagiosum of the eyelids 10/65 (15%) and Herpes Zoster Opthalmicus (HZO) (12).

In a study in Uganda at New Mulago Hospital on HIV/AIDS patients presenting with conjunctival squamous cell carcinoma and carcinoma in situ, it was noted that 36 cases (75%) were HIV positive. HIV seropositivity was statically significant p 0.005. The mean age was 32.5 years and the male female ratio was approximately 1:1. The tumour occurred more frequently in the young adult between 20-35 years old (13).

In Kenya, Chisi et al in a cross sectional study on 409 HIV positive patients at Kenyatta National Hospital and Kikuyu Eye found a prevalence of conjunctival squamous cell carcinoma of 7.8% (14).

Another Study in Kenya by Saudo et al, found that 100% of a consecutive series of patients with HZO who were younger than 47 years of age had HIV antibodies (31). The presence of HIV infection in patients with HZO correlated well with the severity of corneal involvement and post- herpetic neuralgia (16). Msosa et al found HZO in 0.8% of the patients attending an eye clinic at Kenyatta National Hospital (28). Nwosu et al conducted a study to determine the incidence and pattern of ocular findings in HIV/AIDS patients in Nigeria. 1011 patients were examined over a 6 years period. The median age of patients was 31 years and HZO was found to be the commonest ocular manifestation at 46% (26).

 

2.1.2 Anterior Segment Manifestations

The anterior segment includes the cornea, anterior chamber and iris. Cunningham et al noted that the most common visually important complications include dry eyes (keratoconjunctivitis sicca), cornea infection (keratitis), and anterior chamber inflammation ( iridocyclitis) (8). Differences in the prevalence have been reported in different parts of the World.

In Cameroon, Mvogo et al, found anterior segment abnormalities in 30% of their HIV/AIDS patients(17). The principal lesions of the anterior segment were herpetic keratitis (10.5%) and herpes zoster ophthalmicus (12.3%) (17).

Ndoye et al in Dakar noted a prevalence of 52% of ocular manifestations in HIV/AIDS patients. Patients with CD4 counts greater than 400 had conjunctivitis, herpes zoster keratitis, and ocular dryness. The only ocular lesion in patients with CD4 counts between 200 and 400 was ophthalmic herpes zoster. 77.14% of HIV infected patients with ocular lesions were infected with HIV-1 (18). The three ophthalmic herpes zoster cases were less than 30 years and homosexual. 

In Mali they studied visual impairment in a socially and professionally active population attending the tropical ophthalmology institute of Africa (IOTA). Eight hundred and twenty eight patients ranging from eighteen to fifty years of age, underwent thorough ocular examination. Bilateral blindness was observed in 5.8% of cases. The main cause of bilateral blindness was immune recovery uveitis and cataract (19.2%) (19).

2.1.3 Posterior-Segment Manifestations

The posterior segment includes the retina, choroid, and optic-nerve head. More than half of HIV-positive patients have disorders involving these structures(10). Diagnoses are usually based on characteristic clinical findings observed on dilated fundus examination with the use of either a direct or an indirect ophthalmoscope.

 Posterior segment findings as noted by Cunningham in a review article included HIV associated retinopathy and a number of opportunistic infections of the retina (CMV Retinitis,  VZV retinitis, Toxoplasmic retinochoroiditis, bacterial and fungal chorio-retinitis ) and infectious choroiditis (8).

Mvogo at al in Cameroon examined HIV 1 and HIV 2 patients. Ocular lesions were observed in both HIV-1 and HIV-2 positive patients; however they were much more common in the former group (77.1%).  Ocular pathology was found in 36 patients (36%). The most common posterior segment lesions in their study were CMV retinitis (14%) and uveitis (15.8%(17).                             Jabs et al at John Hopkins in the USA studied the ocular manifestations in patients on HAART. Evidence of intraocular inflammation was substantially more common among patients with CMV retinitis or other major ocular complications than among those without, as were the complications of infection and inflammation. Macular oedema and epiretinal membrane formation were most common among patients with long-standing retinitis and immune recovery(20).

In Ethiopia, Giorgis et al in a study  in the armed forces found uveitis and CMV retinitis in 4 out of 65 patients (6.2% each) (12). In Gambia Jaffar et al found no cases of CMV retinitis but cotton wool spots were noted and their conclusion was that CMV retinitis is less common in Gambia than in developed countries (21).

In Malawi, Beare et al studied patients with concurrent infections of HIV/AIDS and tuberculosis. They noted that in Malawian patients with TB presenting acutely with fever, choroidal granulomas were found in 2,8% of patients (22).

2.1.4 Neuro-Ophthalmic Manifestations

Cunningham et al in their review noted that papilloedema from elevated intracranial pressure, cranial nerve palsies, and ocular motility disorders are significant findings in patients with HIV/AIDS.  Visual field defects have also been reported (8). Assefa at al conducted a study to describe the ocular manifestations of HIV/AIDS documented at Gondar University Hospital in a cross sectional study on one hundred and twenty five HIV/AIDS patients. Neuro-Ophthalmic disorders were found in 9.6 % (29).

Copeland et al noted that neuro-ophthalmological manifestations are not necessarily a marker of the disease severity although some sight threatening eye disease in AIDS patients occur at late stage in the disease when the immunity has been severely compromised ( CD4 cell count<100/mm³ (6).

2.2              Association between Ocular Manifestations and CD4

 

The pattern of ocular manifestations in HIV/AIDS patients observed in different studies seem to suggest that it is related to the CD4 count (16).

Giorgis et al in a cross sectional study in Ethiopia assessed the visual impairment caused by HIV/AIDS related ophthalmic lesions in relation to CD+T lymphocyte count. A total of 186 patients were examined with CD4+ T lymphocyte counts ranging from 1 to 200 cell/micro. 32,8% were found to have HIV/related ophthalmic lesions. Eleven were unilateral blind and two were bilateral blind. The leading cause of blindness was CMV related lesions and was higher among cases with CD4+T lymphocyte count of 50 and below. The likelihood of having HIV/AIDS related lesion was higher among cases with CD4+ T-lymphocyte count of 50 and below. The presence of visual threatening ophthalmic lesions in highly immunocompromised AIDS patients shows the importance of early detection and treatment (12).

Mvogo et al in Cameroon conducted a study to identify ocular complications of HIV/AIDS to determine any correlation with the level of CD4+T lymphocytes. A total of fifty seven patients were examined. The mean age was 38.9 years. 91.7% of the patients with ocular complications had a CD4 count of less than 200/mm³. A linear correlation was found between the CD4 level and ocular complication of HIV/AIDS. It was also noted that with improved access to antiretroviral treatment, ocular complications of HIV/AIDS become more common (17).

Ndoye et al in Senegal noted that 62.5% of AIDS patients with a CD4 count of less than 200 had a normal ophthalmological examination. In patients with CD4 counts between 0 and 200 (27%) had macular oedema, hyalitis, cotton-like nodules, retinal uveitis, and microangiopathy, while those with higher CD4 counts had none of these ocular lesions. In this study the overall prevalence of ocular manifestations was 52% (18).

Cochereau et al in Burundi suggested that the prevalence of ocular manifestation in AIDS patients in Africa is far lower than that in Europe and USA, possibly because most patients die before ocular opportunistic manifestation occur (23).

 

Ah-Fat et al suggested that with the improvement of treatment and patients’ survival, ophthalmic complications are now being seen with increasing frequency in AIDS, occurring in up to 75% of patients during the course of the disease (25).

 

In the USA in 1998 a study was conducted to determine whether the maintenance therapy can be discontinued in patients with quiescent CMV retinitis and increased CD4 count after active treatment with highly active anti retro therapy (HAART). The results showed that discontinuation of therapy may be considered in patients with HAART induced elevated CD4 count above 100 cells /uL (24).

 

 

 


3.0       OBJECTIVES

3.1      Broad Objective

To determine the prevalence and pattern of ocular manifestations in adolescents and adults with HIV/AIDS at MTRH (AMPATH clinic).

3.2      Specific Objectives

1. To determine the prevalence of ocular manifestation in HIV/AIDS patients attending HIV/AIDS care clinic (AMPATH).

2.  To determine the association between ocular manifestations and CD4+ T lymphocyte count in patients with HIV/AIDS.

3.  To determine the association between ocular manifestations and systemic diseases in patients with HIV/AIDS.

 

 

 


4.0       METHODOLOGY

4.1.       Study Design:

A cross sectional hospital based study.

4.2       Study Population:

 Adolescents and adults with HIV/AIDS attending AMPATH clinic.

4.3        Eligibility Criteria:

4.3.1    Inclusions Criteria:

 -  Patients diagnosed with HIV/AIDS attending AMPATH clinic. The diagnosis made in AMPATH clinics was based on ELISA test results.

 -  All patients of aged 15 years and older were recruited into the study. The age of 15 was considered a cut off point for adolescents in this study. This cut off point has been used in most HIV/AIDS studies as it is considered the age at which most subjects are sexually active.          

- Patients who gave written informed consent. In patients too young to give consent this was obtained from their parents or guardians.

4.3.2    Exclusion Criteria

  HIV seronegative patients and those who refused consent.

 4.4     Sample Size

 Sample Size Justification:

The sample size was determined by the following formula:

 

n          =          Z2crit * P (1-P)

                                    D2

Where n = required sample size,

P = prevalence of the population set at 0.3,

 D = Precision of the Study set at 0.1 (10%) and

Both Zcrit is the cut off points along the x-axis of the standard normal probability distribution that represents probabilities matching the 95% confidence interval (1.96).

Substituting the above in the formulae we get;

n                   121.01

=          121 patients

This formula was chosen because the study design of this study is a cross sectional  hospital based study.

4.5      Study Setting

The study was carried out in Eldoret at MTRH (AMPATH clinic).

4.6      Study Period

3 weeks from 31 March to 21 April 2008.

4.7      Data Collection

 The data was recorded on a well structured questionnaire. Care was taken to minimize the risk for missing and erroneous data. Data was then cleaned and entered on a specially designed SPPS data analysis sheet.

4.8      Data Analysis

Data analysis was done using SPSS version 12.0. A p- value of less than 0.05 was considered statistically significant.

4.9              Materials

The following material was used:

·         A formulated questionnaire.

·         Pens and books.

·         Torches/spotlights with batteries and spares bulbs.

·         Snellen chart literate and illiterate.

·         Slit lamp.

·         Direct and indirect ophthalmoscope

·         Loupes +20, +90 Ds

·         Mydriatics: tropicamide,  mydriatic cocktail, cyclopentolate.

·         Pencils( colored)

·         Scheme and sheet for fundus drawing

·         Spirit

·         Dry gauze

·         Gloves

4.10.   Procedures

 

Patients were randomly recruited daily from the AMPATH clinic. On average, about 100 patients were seen every day. Daily, only 20 patients were randomly selected for the study. Upon arrival at the clinic patients were allocated numbers from 1 to 100. The first patient (number 1) was picked, followed by every other 5th patient (i.e. patients number 5, 10, 15, etc). The aims and the procedures of the study were explained and those who consented to participate were examined. The ocular examination had the following format:

-           Visual acuity test: Snellen chart

-           Color vision test: Ishihara test

-           Tonometry: Goldmann applanation

-           Anterior segment examination : slit lamp

-           Dilated fundus examination with mydriatics: 90 D slit lamp biomicroscopy and 20 D binocular indirect fundoscopy.

The medical records of the patients were used to obtain information on systemic diseases, HIV status, CD4 counts and use of antiretroviral therapy.

4.11.   Limitations

 

Potential bias in measuring predictors:  CD4-count is considered a reliable predictor of ocular manifestations. However, the lower limit for CD4 count to predict ocular involvement in HIV/AIDS is difficult as some patient may have ocular manifestations with a normal CD4-count.

Laboratory tests like CD 4 counts, renal function tests and histology for conjunctival tumours had already been done where appropriate. It was therefore difficult to confirm some diagnosis or get the new tests if needed. Some patient had tumours in situ and diagnosis was made based on clinical judgement.

The study period was short and was preceded by post election violence . This could mean that the cases we saw were the very sick ones who needed urgent treatment.

 

4.12.     Ethical issues

 

·                     The Institutional research and ethics committees (IREC) were informed and appropriate approval was obtained.

·                     Informed consent (both verbal and written) was obtained from all participants. For subjects not capable of giving informed consent, surrogate consent was obtained.

·                     Anonymity was ensured by using an anonymous case form which was filled by the investigators.

·                     Results were communicated to the patients and appropriate treatment was instituted where necessary.

·                     Confidentiality and privacy was maintained throughout the study. Data was stored savely and only made accessible to the researchers.

·                     There was no gender or racial biases.


5.0       RESULT

 

Table 2: Baseline Data of the Study Patients (n = 200)

Factor                    Frequency, n (%)                         Mean (SE)                   Median            IQR

Age (years)                 -                                               38.65 (±0.74)               36.0                 (32 –44)

15 - 24                           9 (4.5)

25 – 34                        71 (35.5)

35 – 44                        72 (36.0)                                  -                       -                       -

45 – 54                        30 (15.0)

55 – 64                        13 (6.5)

64 +                               5 (2.5)

Sex

Male                              68 (34.0)                                -                       -                       -

Female                         132 (66.0)

 

The mean age of the study participants was 38.65 years with a standard deviation of 0.74. The median was 36.0 yrs and the interquantile range was 32 – 44 years.  There were more females (66%) recruited as compared to males (34%).
 Figure 2: Distribution by Sex (n = 200)

 

The ration of females to males was 2:1.

 

Figure 3: Distribution by Level of Education (n=200)

More patients had a primary school level of education.

Figure 4: Distribution by Age (n = 200)

Most of the participants were in the age group between 25 yrs and 44 years (71.5%).
Figure 5: WHO Visual Acuity Classification in Better Eye (n = 200)

Five percent of the study participants were blind in this study based on the WHO ICD – 10 classifications. All the five patients with CMV retinitis had bilateral involvement and all of them were in WHO category of blindness. Also in this group were patients with bilateral optic atrophy and some with bilateral chorioretinitis. Severe visual impairment and visual impairment were mostly due to a combination of anterior and posterior segment features.

 


Figure 6: Prevalence of Ocular Manifestation among patients HIV/Aids (n =200)       

The overall prevalence of ocular manifestations was 77% in the AMPATH HIV/AIDS patients.


Figure 7: Pattern of Ocular Manifestation (n = 200)

Most ocular manifestations were noted in the posterior segment (53%). In the anterior segment, iridocyclitis was predominat in patients with posterior segment findings such as retinal microangiopathy and chorioretinitis.
Table 3: Ocular Examinations: Summary of Findings (n = 200)

Ocular Examination

Frequency

Percentage

Color Vision

Normal

Abnormal

 

186

  14

 

93.0

7.0

Extra Ocular Motility

Free

Restricted

 

198

    2

 

99.0

1.0

Adnexal Manifestation

Normal

HZO

KP

SCC

Conj. Microvasculopathy

Conjunctival Growth

Molluscum Contagiosum

 

148

  12

  10

  13

    9

    3

    5

 

74.0

6.0

5.0

6.5

4.5

1.5

2.5

Anterior Segment Manifestation

Normal

Keratoconjuctivitis sicca

Infectious keratitis

Iridocyclitis

Pupil/Iris: Fibromembrane

 

 

127

     1

     3

   11

   37

 

 

63.5

0.5

1.5

5.5

18.5

 

Posterior Segment

Normal

Retinal Microvasculopathy

CMV

Chorio Retinitis

Vitreous opacity

Perivasculitis

Macular Oedema

 

 94

75

5

9

8

1

8

 

47.0

37.5

2.5

4.5

4.0

0.5

4.0

Neuro Ophalmology

Normal

Optic Atrophy

Papilloedema

Papillitis

 

189

3

4

4

 

95.5

1.5

2.0

2.0

 

Two cases of papilloedema and 2 cases of papillitis were attributed to cryptococcal meningitis.

 

 

 


Figure 8: Adnexal Findings (n = 52)

The conjunctival growths noted were suspicious lesions. They were not degenerations like pingueculas. Squamous cell carcinoma confirmed by histology was noted in 5.8% of the patients.

 

 

 

 

 

 

 

 

Figure 9: Anterior Segment Findings (n = 52)

Cyclitic pupillary membranes were the commonest anterior segment finding (50.7%).  The diagnosis of acute simplex keratitis was based on the clinical picture.

Figure 10: Posterior Segment Findings (n = 103)                                  

Signs of retinal microvasculopathy noted included cotton wool spots, retinal dot and flame shaped haemorrhages.

Figure 11: Neurophthalmology Findings (n = 11)

Eleven patients were noted to have neuro – ophthalmologic findings. Two cases of papilloedema and 2 cases of papillitis were attributed to cryptococcal meningitis. No clear cause could be identified in the other cases.

 

 


Figure 12: Systemic Manifestation (n = 81)

Tuberculosis was the commonest systemic finding in the study participants. Over half (53.1%) of the patients were on TB treatment.


Figure 13: Level of Current CD4 Count (n = 200)

Twenty seven percent of the participants had a current CD4 count of  ≤200 cells/microliter.


Figure 14: HIV/AIDs Staging (WHO Classification; n = 200)

Forty one percent of the participants were in stage III and IV as graded by the AMPATH physicians. By definition, these are patients all eligible for HAART by WHO recommendations.


Table 4: ARV Treatment (n = 200)

Status                                                           Frequency (n)                            Percentage (%)

On ARVs:                                                      

Yes                                                                  118                                          59.0

No                                                                                 82                                          41.0

 

ARV Drugs:

·         AZT     (Zidovudine)                              35                                          29.7

·         3TC     (Lamivudine)                           104                                          88.1

·         D4T     (Stavudine)                                53                                          44.9

·         DDZ    (Didanosine)                                2                                            1.7

·         ABC    (Abacavir)                                   5                                            4.2

·         NVP     (Nevirapine)                              65                                          55.1

·         EFV     (Efavirenz)                                34                                          28.8

·         NFV     (Nelfinavir)                                  4                                            3.4

 

ARV Dug Combinations:

·         Four drugs                                               6                                            5.1

·         Three drugs                                            69                                          58.5

·         Two drugs                                              28                                          23.7

·         One drug                                                15                                          12.7

 

Most of the patients were on a three drug combination (58.5%).
Table 5: Association between Ocular Manifestation and Current CD4-Count (n = 200)

Factor                         Ocular Manifestation, n (%)              OR 95%CI                 p-value

CD4-Count       (n)

    0 – 100    22                  21 (95.5)                                  5.7   (0.77 – 117.30)    0.044

101 – 200    32                  31 (96.9)                                  9.1   (1.26 – 184.14)    0.021

201 – 300    30                  26 (86.7)                                  1.7   (0.51 –     6.12)    0.500

301 – 400    33                  38 (75.7)                                  0.9   (0.33 –     2.45)    0.975

401 – 500    37                  28 (75.7)                                  0.7   (0.28 –     1.79)    0.975

500 +         46                    29 (63.0)                                  0.28 (0.13 –     0.64)    0.001

There was a significant association between current CD4 count of between 0 – 100, 101 – 200 and 500+ and ocular manifestations with a p-value of less than 0.05. Participants with CD4 counts of between 0 – 100 were 5.7 times more likely to have ocular manifestations than participants with CD4 counts of >100.

 

 

 

 

 

 

 

 

 

 

 

Table 6: Association between Ocular Manifestation and Systemic Disease (n = 200)

Factor                         Ocular Manifestation, n (%)              OR 95%CI                 p-value

Systemic Disease         (n)

TB                         43                    35   (81.4)                                1.1 (0.27 –   4.19)        0.844

OPC                       19                    19   (84.2)                                1.0 (0.22 –   5.38)        0.641

ETB                         6                      5   (86.7)                                1.0 (0.10 – 23.05)        0.593

Enteropathy                         4                      3   (75.0)                                0.7 (0.10 – 19.21)        0.593

Recurrent HZ          3                      3   (75.7)                                            -                                   -

PGL                         3                      3   (75.7)                                            -                                   -

Meningitis                            2                      2 (100.0)                                -                                   -

KS                           1                      1 (100.0)                                -                                   -

There was no significant association between the systemic disease status and ocular manifestations (p > 0.05). However, patients with TB were 1.1 times more likely to have ocular manifestations.

 

Table 7: Association between Adnexal Findings and Current CD4 count (n = 52)

CD4 Count      n          HZO    KS       SCC   Conj*. Micro. ** Conj.* Growth    Molluscum

   0 – 100           2        -           1          -                       1                      -                      

101 – 200        12        -           3          3                      3                      1                      2

201 – 300          6        2          2          1                      1                      -                       -

301 – 400          9        3          1          3                      1                      -                       1         

401 – 500        11        3          3          2                      1                      1                      1

500 +               12        4          -           4                      2                      1                      1

*Conj.                         Conjunctival

**Micro.          Microvasculopathy

No significant association was observed between current CD4 count and adnexal findings (p = 0.803)

Table 8: Association between Posterior segment Findings and Current CD4 count (n = 106)

CD4 Count      n          Ret.M.*     CMV      Cho. **     V.Strand         PV***       Macu.Oedema****

    0 – 100        (20)      11                    5          2          1                      -                       1

101 – 200        (23)      16                    -           3          2                      1                      1

201 – 300        (15)      11                    -           1          1                      -                       2

301 – 400        (16)      12                    -           2          2                      -                       -

401 – 500        (18)      12                    -           1          1                      -                       4

500 +               (14)      13                    -           -           1                      -                       -                      

* Ret.M.                                                Retinal Microvasculopathy

**     Cho.                              Choroidopathy

***   PV                                 Perivascular Sheathing

****Macu.                           Macular

There was a significant association between current CD4 count and posterior segment findings (p=0.040).  CMV retinitis was noted only in patients with a CD4 count of less than 100 while retinal microvasculopathy was seen in patients with higher CD4 counts.


Table 9: Association between Ocular Manifestation WHO staging and ARV Treatment (n = 200)

Factor                         Ocular Manifestation, n (%)              OR 95%CI                 p-value

On ARV                       (n)

Yes                        (118)                106 (68.8)                    6.3 (3.0 – 13.1)                        <0.001

WHO Stage

I                             (72)                  48 (66.7)

II                            (46)                  37 (80.4)                                  -                       <0.001

III                          (59)                  54 (91.5)

IV                          (23)                  22 (95.7)

There was a significant association between ocular manifestation, patients on ARV and WHO staging with p< 0.001. Patients who were on ARV were 6.3 times likely to have ocular manifestations.

Table 10: Factors associated with Presence of Ocular Manifestations (n = 200)

Factor                         Parameter Estimates              Std. Error                   P-value

Age                                          0.068                           0.024                           0.004

Levels                                                                                                                                                     

     AZT use                              -2.99                            1.36                             0.028  

    On ARV                              -4

 

On logistic regression only age (p=0.004), AZT (p=0.028) and ARV (p=0.029) usage were significant as shown in the table above.

 

6.0       DISCUSSION

In this series at AMPATH clinic in Western Kenya, a total of 200 HIV/AIDS patients were recruited and examined.

STUDY POPULATION

All participants were out patients in fair general condition. They were on follow up and on management for HIV/AIDS in the AMPATH clinic.

The age range was 16 years to 74years with a mean age of 38.65 (±0.74) years.  More than 70 % of the patients fell in the 25-44 years age group (Table 1) considered the high risk group for HIV infection. This age distribution could be explained by the mode of spread of HIV in Kenya. Heterosexual infection is the commonest mode and this age group is the most sexually active.  Female to male ratio was 2:1, females constituting 66%.In the AMPATH clinic register females account for about 65% of their patients. This finding could be due to the slightly higher prevalence of HIV in females than males. Females also accept their status more easily than males hence they seek health care more often as noted by Griensztejn et al (32).

In terms of level of education 20.5 % of the patients had not attended school at all, 49 % had achieved primary level of education, 28 % had secondary education and only 5 % had any form of tertiary education (Table 1). It is important to point out that education not only affects changes in sexual behaviour, but also predicts level of knowledge about the disease. A study based on data from the 1998–1999 National Family Health Survey (NFHS) of India found that the higher the level of education of women, the more likely it is that they will have greater awareness of and accurate knowledge on AIDS. Another significant result from this analysis was the importance of informal learning in rural areas: women’s knowledge of AIDS depended on interaction with people of equal or higher education levels (30).

 

Visual acuity was normal in 65 % of the patients, 20 % had visual impairment, 10 % severe visual impairment and 5 % were blind by WHO standards (Figure 3). The significant causes of blindness were bilateral fulminant CMV retinitis involving the macula and optic nerve atrophy. In Ethiopia, Giorgis et al also noted that the leading cause of blindness was CMV retinitis. They also noted HZO as a significant cause of unilateral blindness (12).

OCULAR MANIFESTATIONS

It was noted that 77 % of the patients had some form of ocular manifestations. These findings are close to the results noted in Cameroon (63.2%) by Mvogo et al (17).  In Dakar, Senegal Ndoye et al found a prevalence of 52.3 % (18). In Ethiopia, Giorgis et al found ocular manifestations in 32.8% (12).  The higher prevalence noted in this study is probably due to the fact that 93% of the patients were on ARVs which is high as compared to the studies above. Mvogo et al actually pointed out that with improvement of access to antiretroviral therapy; the ocular manifestations of HIV/AIDS become more common. ARVs are also indicative of severe disease on initiation of the systemic therapy in patients with low CD counts.

In a review article by Al- Fat et al they noted that ocular manifestations may occur in about 75% of HIV/AIDS patients in the course of their disease (25) and suggested that with improvement of treatment and patients survival, ophthalmic complications are now being seen with increasing frequency in AIDS, occurring in up to 75% of patients during the course of the disease.

Ocular findings in this study were more common in the posterior segment (53%), followed by the anterior segment (26.5%). Adnexal manifestations were noted in 26.5 % of the patients and neuro ophthalmic manifestations in 11 % (Figure 5). This is consistent with Jabs et al observations in the USA who also noted that intraocular inflammation and other posterior segment manifestations is becoming a predominant feature with the exception of CMV retinitis (20).

This study found CMV retinitis in 2.5% of the cases. Findings in other studies range from <1% to 20%. Asseffa et al, in Ethiopia and Cochereau et al in Burundi found 1% while Jabs et al in the USA found in 14%. Balo et al in Togo found the highest prevalence at 21.5%. In Ethiopia, Giorgis et al in a study  in the armed forces found uveitis and CMV retinitis in 4 out of 65 patients (6.2% each) (12, 29). In Gambia Jaffar et al found no cases of CMV retinitis but cotton wool spots were noted and their conclusion was that CMV retinitis is less common in Gambia than in developed countries (21). These varied findings in the prevalence of CMV retinitis could be explained by the study design, the sample size and the effects of ART on the CMV virus. There is a substantial decline in the incidence of CMV retinitis from the pre-HAART era. (20).

Retinal microvasculopathy was the most common posterior segment finding seen in 37.5% of the patients. Only 2.5% of the patients had presumed CMV retinitis with poor vision and 4.5% had other forms of chorioretinitis apparently not related to CMV. Some of chorioretinal lesions may have been ocular TB as they occurred all in patients on TB treatment. However there were no classical choroidal granulomas (Figure 8). CMV retinitis was noted only in patients with a CD4 count of less than 100 while the HIV microangiopathy was also noted in CD4 counts of greater than 500. Nwosu et al at the Guinness Eye centre in Nigeria found bilateral CMV retinitis in 6% of the patients. The CD4 count was less than 100 in all CMV patients as observed in this study. Assefa et al at Gondar University Hospital in Ethiopia found retinal microvasculopathy in 24% of patients which is less than found in this study (29). Ndoye et al found that patients with CD4 counts between 0 and 200 had macular oedema, hyalitis, cotton-like nodules, retinal uveitis, and microangiopathy, while those with higher CD4 counts had none of these ocular lesions. The only ocular lesion in patients with CD4 counts between 200 and 400 was ophthalmic herpes zoster in Ndoye’s study (18).

 

Anterior segment manifestations were seen in 36.5 % of patients, the most notable being a greyish fibrous membrane attached to the iris mostly near the pupillary margin (18.5% ), followed by  active iridocyclitis (5.5%). Similarly Nwosu et al in Nigeria found iridocyclitis in 4% of the patients. The membrane could be due to old resolving immune recovery uveitis.

 Mvogo et al in Cameroon found anterior segment abnormalities in 30% of their HIV/AIDS patients (17). The principal lesions of the anterior segment in their study were herpetic keratitis (10.5%) and HZO (12.3%). In this study membranes in the pupillary area were the most predominant feature in the anterior segment. This could be due to frequent recurrent uveitis episodes which have been reported as immune recovery ocular inflammation in HAART patients. Herpes Zoster Ophthalmicus accounted for 6% of the ocular findings in all HIV/AIDS patients in this study. Most of them had both lid involvement and corneal involvement. The highest prevalence of HZO in HIV patients was reported by Nwosu et al in Nigeria at 48%. Msosa et al found HZO in 0.8% of all patients attending an eye clinic at Kenyatta National hospital in Kenya regardless of their HIV status (27). Ndoye et al reported an HZO prevalence of 8.5% in HIV/AIDS patients in Dakar, Senegal (18). This is similar to the findings noted in HIV/AIDS patients at AMPATH clinic in this study.

 Adnexal manifestations were present in 26% of our patients and the main findings were squamous cell carcinoma (6.5 %), HZO (6 %), Kaposi Sarcoma (5%), conjunctival microvasculopathy (4.5%), molluscum contagiosum (2.5 %) and suspicious conjunctival growth (1.5%). The lower prevalence of microvasculopathy noted in this study could be due to the fact that most of the patients were on HAART for a longer duration and the consequent decrease in the viral load may lead to a decline in the vasculopathy.

The prevalence of squamous cell carcinoma in this study was comparable to findings in Chisi et al study. They noted a prevalence of proven conjunctiva SCC of 7.8 % in HIV patients (14). Ten of the SCC were diagnosed clinically while three had histological confirmation. Guech, Ongey et al in the USA found a significantly increased risk for squamous cell carcinoma in patients with HIV/AIDS (28). 

Neurophthalmic findings were seen in 11 patients and included optic atrophy (3 patients), papilloedema (4 patients) and papilitis (4 patients). Assefa Y et al found neuro-ophthalmologic disorders in 9.6% in their HIV/AIDS patients which is similar to this study (29). Two cases of papilloedema and two cases of papillitis were attributed to cryptococcal meningitis based on the clinical appearance and context. However, no other specific causes for neuro-ophthalmologic findings could be established. This is similar to other studies from comparable settings where limited diagnostic capacities often prevent establishing exact causes. These infections are due to the immunosuppression of HIV.

 

Systemic manifestations of HIV/AIDS were seen in 81 patients with TB (53.1 %) and oro-pharyngeal candidiasis (23.5%) being the commonest. In Malawi, Beare et al found TB in 43% of the patients with HIV/AIDS (22). They noted choroidal granulomas in 3% of patients with systemic TB. No choroidal granulomas were found in this study. There is no significant association between systemic diseases and ocular manifestations (Table 4). However, a number of patients with TB and oro-pharyngeal candidiasis were also noted to have ocular manifestations but this was not statistically significant.

In this study most patients were in HIV/AIDS stage I (36 %), followed by stage III (9.5 %), stage II (23 %) and stage IV (11.5%) (Figure 8). Patients in stage IV had the highest prevalence of ocular manifestations (95.7%) followed by patients in stage III (91.5%). The least prevalence was noted in stage I (66.7%). This relation was statistically significant and suggests that the magnitude of the ocular involvement increases with severity of the HIV/AIDS disease (Table 5). The higher magnitude of ocular manifestations in stage I demonstrates that ocular manifestations may occur at any CD4 count. Most of the manifestations in this stage were non-blinding. Assefa et al in their study from Ethiopia reported 90% of the patients in clinical stage III and IV. Of these, 60% had at least one ocular manifestation (29).

CD4 T lymphocyte counts have previously been said to be a reliable predictor of ocular complications of HIV infections (5). This study found that patients with CD4 count less than 100 cells/ml had higher rate (95.5%) of ocular manifestations (p=0.04).

However the study showed no linear association between ocular adnexal findings, ocular anterior segment findings and neuro-ophthalmic findings with the level of CD4 count, but demonstrated a positive association between posterior segments findings (p=0.04).

 

 


7.0              CONCLUSIONS

1.                  The prevalence of ocular manifestations in HIV/AIDS patients as seen at AMPATH clinic was 77%. The most prevalent manifestations were noted in the posterior segment (53.9%). The prevalence of anterior segment manifestations was 26.5% and that of adnexal manifestations was also 26.5%.

2.                  The most common posterior segment findings were retinal microvasculopathy and chorioretinitis while fibrous membrane on the iris and active iridocyclitis were the most common findings in the anterior segment. Though CMV retinitis was noted in only 2.5% of the patients, it was one of the main causes of binocular blindness.

3.                  The commonest systemic finding was pulmonary TB. However, there was no statistically significant relation with ocular manifestations of HIV/AIDS in this study.

4.                  Ocular manifestations of HIV/AIDS are related to both the severity of clinical disease staging (e.g. WHO stages III and IV) and severity of immune suppression (CD4+ count).

5.                  Fifty-nine percent of HIV/AIDS patients were on ARV and among these 93.2% had ocular manifestations.

 

 

 

 

 

 

 


8.0       RECOMMENDATIONS

 

1.                  There is need for routine referral for ophthalmic evaluation of HIV positive patient in WHO stages III and IV and / or severe immune suppression (CD4+ count levels less than 200 cells/ml).

2.                  There is need for early and appropriate management of immune recovery related eye disease as evidenced by the high rate of old and active cyclitis in our patients from presumed immune recovery uveitis.

 

 

 

 

 

 

 

 

 

 

 

 9.0.      REFERENCES

 

1.      Lisa M.Krieger, Oldest AIDS case found with blood sample containing virus: The san Francisco examiner, February,3,1998. AEGIS-SFE

2.      Hymes, K.B. Griene, J.B, Marcus, A, et al. Kaposi sarcoma in homosexual men: a report of eight cases, 1981, Lancet vol2 1981,:

3.      Welfer IV et al. HIV infection and AIDS; Oxford Textbook of medicine ( third edition) Oxford, Medical publications 1996:pp.467-483

4.      WHO/GPA. Clinical management guidelines for HIV infection in adults. Preliminary document, April 1991

5.      UNAIDS/WHO report on the global HIV/AIDS epidemic. Geneva: World Health Organization, December 2003

6.      Copeland, Robert et al: Review of ocular manifestations of HIV, Ophthalmology 2005, Oct;114(12): 1453 - 9             

7.      National AIDS/STD control programme (NASCOP): Research monitoring and evaluation unit Ministry of health. 2003 National HIV surveillance.

8.      Cunningham ET Jr, Margolis TP et al:  Ocular manifestations of HIV infection. New Engl J. Med 1998;Vol 339:236-44.

9.      Hung, Fan et al : AIDS, Science and Society, third Edition, Jones and Bartlett publishers, Inc.2005; 45.

10.  Holland GN, Gottlieb MS, Yee RD, et al. Ocular disorders associated with a new severe acquired cellular immunodeficiency syndrome. Am J. Ophthalmology 1982; Vol 93:393-402

11.  Lewallen S. Herpes zoster ophthalmicus in Malawi. Opthalmology 1994; Vol 101:1801-04

12.  T/Giorgis A, Melka F,G/Morion A. Opthalmic manifestations of AIDS in Armed Forces General Teaching Hospital, Addis Ababa. Ethiop Med J. october 2007: vol 45(4):327-34

13.  Albert, Cook et al, HIV/AIDS at Makerere medical school, Kampala, UGANDA. WHO public health bulletin, Nov 2004.

14.  Chisi SK, Kollman, Karimurio J. Conjunctival Squamous Cell Carcinoma in patients with human immunodeficiency virus infection at two hospitals in Kenya. East Africa Med Journal. 2006 May: Vol 83(5): 267-70

15.  Saudor E.V, Millman. A. and Croxson T.S et al. Herpes Zoster Opthalmicus in patients at risk for the acquired immune deficiency syndrome. Am.J.Opthalmol.1986; Vol 101;53-55.

16.  Biswas J, Madhavan HN, George AE, et al. Ocular lesions associated with HIV infection in India: a series of 100 consecutive patients evaluated at a referral center. Am J Opthalmol 200; Vol 129:9-15.

17.  Ebana Mvogo C, Ellong A, Bella AC, Lumah A Chu Jokoh. Ocular complications of HIV/AIDS in Cameroon: Is there is any correlation with the level of CD4 Lymphocyte: Bull soc Belge Opthalmo,2007: Vol (305):7-12

18.  Ndoye N.B, Sow PS, Ba EA, Ndiaye MR, Wade A, Coll-seck AM. Ocular manifestatios of AIDS in Dakar. Dakar med 1993; Vol 38(1):97-100

19.  Miles: Extent of visual impairment in a socially and professionally active population attending the tropical ophthalmology institute of Africa (IOTA).Tropical medicine bulletin. 2006 october: Vol 66(5):447-60.

20.  Jabs DA, Van Natta Ml, Holbrook JT, Kempen JH, MEINERT CL, DAVIS MD. Studies of the ocular complications of AIDS: Ocular diagnoses at enrollement. Opthalmlogy 2007 Apr 114(4):780-6.

21.  Jaffar S, Ariyoshi K, Frith P, Okouchi Y, Sabally S, Ajewole T, Bailey R, Lee PS, Corrah, Johson G, Faai H, Whittle H. Retinal manifestations of HIV-1 and HIV-2 infections among hospital patients in the Gambia, West Africa Trop. Med (int) Health 1999 july: Vol 4(7):487-92.

22.  Beare NAV, Kublin JG, Lewis DK, MJ Schijffelen, KPH Peters, G.Joak, J.Kumwenda. Ocular disease in patients with tuberculosis and HIV presenting with fever in Africa. British journal of Opthalmology 2002; Vol 86:1076-1079.

23.  Isabelle Cochereau, Najoua Mlika-cabanna, Philippe godinaud,Theodore Niyongabo, Bernard poste. AIDS related eye disease in Burundi, Africa. British J. Opthalmol Vol 199:83:339-342

24.  Jyotirway Bismas, Hagie N.Madham, Amola E.George, N.Kumarasany and Salamon. Ocular lesions associated with HIV infections in INDIA. American J.Opthalmolol2000: Vol 129, 9-15.

25.  Ah-Fat Fg, Balterburg M. Opthalmic complications of HIV/AIDS . Postgrad Med J.1996 Dec; 72(854):725-30.

26.  Nwosu NN. HIV/AIDS in  Opthalmic patients: the Guiness Eye Centre Onitsha experience. Nigeria post grad Med Journal. 2008 Mar: Vol 15(1):24-7

27.  Msosa, Adala, Kollmann .Prevalence, Complications and associations of Herpes Zoster Opthalmicus at Kenyatta National Hospital. MMed dissertation 1999, University of Nairobi.

28.  Guech-Ongey M, Engels EA, Goedert JJ, Biggar Rj. Elevated risk for squamous cell carcinoma of the conjunctiva among adults with AIDS in the United States. International  Journal of Cancer. June 2008: Vol 122(11): 2590-3

29.  Assefa Y, Yohannes AG,  Melese A. Ocular Manifestations of HIV/AIDS patients in Gondar University Hospital, North West Ethiopia. Ethiopia Journal of Health Development, 2006: 20(3): 166-169.

30.  Aggarwal, R.M and Rous, j.j. 2004. Know AIDS For No AIDS: Determinant of knowledge about AIDS among women in India. India J of Medicine. 2004. Vol 102: 1526 – 34.

31.  Saudor EV, Millman A, Croxson TS. Herpes Zoster Ophthalmicus in patients at risk for the acquired immunodeficiency syndrome (AIDS). Am. J. Ophthalmology. 1986; 101:53 – 55.

 



 

 

 

 

 

 

 

 

10.0. APPENDIX 1: QUESTIONNAIRE.

 

A) DEMOGRAPHIC DATA.

  1. File No.:…………..
  2. Date of birth………….
  3. Age…………..
  4. Sex:            Male .

                                Female.

  1. Weight…………..
  2. Nationality……………..

 

  1. Have you ever attended school? :          Yes .

                                                                            No.

  1. If yes, how many years of school have you completed?.  ..........years

 B) EYE EXAMINATION

  1. Visual acuity:

¨       ≥6/18 – 6/6     

¨       ≤ 6/18 – 3/60  

¨       ≤ 3/60 – NPL  

 

  1. Color vision     normal       abnormal
  2. Extra ocular motility     free          restricted
  3. Adnexal manifestation:

¨        -Herpes zoster opthalmicus.

¨       -kaposi sarcoma.

¨       -squama cell carcinoma.

¨       -conjunctival microvasculopathy

¨        -. Conjunctival growth

  1. Anterior segment manifestation:

                -keratoconjunctivitis sicca

               -Infectious keratitis

               -Iridocyclitis--- -Keratic precipitates

                         - Flare

                                            -Cells

 

13- Posterior segment manifestation:

                 -retinal microvasculopathy

                  -Cytomegalovirus retinitis

                  -Chorio retinitis                          

                  -Endophthalmiti

                  -Vitreous haemorrhage

                  - Perivascullitis

                  -Macula oedema              

14-Neuro ophthalmology manifestation:

                 -Optic atrophy

                  -Papilloedema

                 -Papillitis

15-Orbital manifestation:

                 -Orbital cellulites

                  -Orbital tumor

 

C) SYSTEMIC MANIFESTATIONS (OI’s);

                   -Pulmonary tuberculosis

                   -Oro pharyngeal candidiasis

                  -HIV enteropathy

                   -Cryptococcal meningitis

                   -Extra pulmonary tuberculosis

                  -Persistent generalized lymphadenopathy

                  -Recurrent zoster dermatitis

                   -Kaposi’s sarcoma

                  -                                                 

TEST:

16-CD4+ count:  0 -50

                           51 – 100              

                           101 – 200

                           201 -300

                           301 – 400

                           401 – 500

17-Current WHO stage:

                 1         2          3        4

18.  Is the patient currently taking, or has the patient ever taken, any of the following antiretroviral medications?

        Yes          no

19.  If yes fill the box next to each medication:

¨       -Zidovudine ( azt) 

¨       -lamivudine (3tc) 

¨       -Stavudine (d4t)   

¨       -Didanosine (ddz) 

¨       -Abacavir (abc)    

¨       -Nevirapine (nvp) 

¨       -Efavirenz (efv)    

¨       -Nelfina (nfv) 

¨       -Others           

20.When did you start ARV’S……..

21. Any relevant past medical history………………………………………

 

 


8.1. APPENDIX 2: PARTICIPANT’S CONSENT FORM

I_______________________________________________________________________

Of   ______________________________p.o box______________________________

Hereby acknowledge that the aims and purpose; procedures, benefits, and risks of this study have been explained to me.

I confirm that I have voluntarily agreed to participate in the study being carried out on ocular manifestation in HIV/AIDS.

 

Signature/thumb print of respondent:  __________________________________

                                                                        Date:  ________________________________

Signature of doctor/researcher:  __________________________________

                                                            Date:  ________________________________

 

 


10.3. APPENDICES 3: Classification of HIV (5)

 

A. WHO classification

¨       Stage1:  -asymptomatic HIV infection

  -persistent generalized lymphadenopathy

 

¨       Stage 2: - herpes zoster (within the last 5 years)    

-minor micocutaneous manifestation

-recurrent upper respiratory tract infection

-weight loss<10% of body weight

¨       Stage 3: -severe bacteria infection( pneumonia)  

-oral candidacies ( thrush)

-unexplained chronic diarrhea (>1month)

-oral hairy leukoplakie

-unexplained prolonged fever intermittent constant (>1month)

-tuberculosis, pulmonary (within previous years)

-weight loss>10% of body weight

¨       Stage 4:  -candidacies( esophageal, bronchi, tracheal)

                   -cryptococcus, extrapulmonary

                   -cryptosporiosis with diarrhea

                   -CMV virus disease

                   -herpes simplex

                   -HIV encephalopathy

                   -HIV wasting syndrome

                   -kaposi sarcoma

 B.  CDC classification scheme for HIV disease.

3 Categories based on the CD4+Tlymphocyte  percentage (count per microliter of blood)

Categories 1: >500 cells/mm3 (orcd4%.24%)

Categories 2: 200-499cells/mm3(or cd4 %<14%-28%)

Categories 3:<200 cells/mm3(or cd4%<14%)

Category A

Consist of one or more of the condition listed below in adolescent or adult >13 years with documentation HIV infection:

-asymptomatic HIV infection

-persistent generalyzed lymphadenopathy

-acute primary HIV infection with accompagning illness or history of acute HIV infection

 

Category B

Consistent of symptomatic conditions in HIV infected adolescent or adult that are not included among condition listed in clinical category C and that meet at least one of the following criteria:

A.The condition is attributed to HIV infection or is indicated of a defect in cell mediated immunity.

B.The condition is considered by the physicians to have a clinical course or to require management that is complicated by HIV infection.

 

 

 

 

 

Category B

 

•Examples of condition in clinical category B include:

-Bacillary angiomatosis

-Candidiasis, oropharyngeal( THRUSH)

-Candidiasis, vulvovaginal, persistent, frequent or poorly responsible to therapy.

-Cervical dysplasia, cervical carcinoma in situ.

-constitutional symptoms, such as fever (38.5) or diarrhea lasting longer than 1 month.

-hairy leukoplakia, oral

-herpes zestier involving at least 2 distinct episodes .

-idiopathic thrombocytopenic purpura

-listeriosis

-Pelvic inflammatory disease

-Peripheral neuropathy

Category C

Includes the clinical condition listed in the 1993 AIDS surveillance case definition.

Once a category c condition ocurred the person remain in category C