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AimsTo determine if early dilated fundus examination for cytomegalovirus (CMV) retinitis leads to better visual outcomes in areas with limited HIV care, where patients may have long-standing retinitis before they are diagnosed with HIV.MethodsTwenty-four eyes of 17 patients with CMV retinitis who were seen at an urban HIV clinic in Chiang Mai, Thailand, were included in this retrospective cohort study. Participants were divided into two groups based on the amount of time from the first documented CD4 count below 100 cells/mm3 to the first eye examination for CMV retinitis. Average visual acuity in each group was calculated at the time CMV retinitis was first detected, and then at 3, 6 and 12 months after diagnosis.ResultsThe group of patients who received an eye examination within approximately 4 months of the initial low CD4 count measurement had better baseline visual acuity (median 20/30,IQR 20/20 to 20/60) compared with patients who presented later (median 20/80, 20/60 to hand motion); p=0.03). Visual acuity did not change significantly during the 12-month study period in either the early group (p=0.69) or late group (p=0.17).ConclusionIn this study, patients who were examined sooner after a low CD4 count had better vision than patients who were examined later. Routine early screening of patients with CD4 counts under below 100 cells/mm3 may detect earlier disease and prevent vision loss.

To evaluate the safety and efficacy of intravitreal injection of liposomes encapsulating infliximab in experimental autoimmune uveoretinitis (EAU) rats.Liposomes containing infliximab were prepared and characterised for mean particle size, entrapment efficiency, polydispersity index (PDI) and zeta potential. In vitro release profile and the stability of infliximab-lip were evaluated. EAU rats were intravitreally injected with saline, infliximab, infliximab-lip or unloaded liposomes. Clinical signs and ocular histological sections were graded. Infliximab concentrations were determined with competitive ELISA. Safety of the intravitreal injections was evaluated by electroretinography (ERG) and histopathological examination. Retinal biodistribution and clearance of rhodamine-conjugated liposomes containing infliximab were evaluated with a laser scanning confocal microscope.The mean particle size of infliximab liposomes was 351.3±58 nm and entrapment efficiency was 90.65%±2.68%. PDI and zeta potential of infliximab liposomes were 0.386 and -20.8±9.78 mV, respectively. Stability test data showed that the infliximab-lip was stable for 60 days at room temperature. In EAU rats, intravitreal injection of infliximab and infliximab-lip greatly reduced intraocular inflammation determined by clinical scores and histopathological analyses (n=4). The mean concentrations of infliximab decreased quickly in infliximab injection group and were lower than those in infliximab-lip injection group (n=4 eyes, p0.05 after 3 days post injection). No retinal toxic effects were detected after intravitreal injection of infliximab-lip in ERG (n=4 rats, p0.05) and histopathological sections compared with normal rats. Confocal microscopy showed that fluorescent liposomes were observed in almost every layer of the retina and remained detectable for30 days after injection.Intravitreal injection of liposomal infliximab can prolong the persistence of the drug in vitreous body and demonstrated a satisfactory safety and significant therapeutic potentials in EAU. The use of biodegradable particles for therapeutic antibody delivery may provide a promising approach for the treatment of ocular diseases.

Aim To evaluate the efficacy of infliximab treatment in patients with refractory uveoretinitis associated with Behcet9s disease. Methods Clinical records of 14 patients were retrospectively reviewed. Patients received infliximab infusions (5 mg/kg) at weeks 0, 2 and 6, and every 8 weeks thereafter. The main outcome measures were frequency of clinically observable ocular inflammatory attacks, background retinal and disc vascular leakage as assessed by fluorescein angiography during periods of clinical quiescence, visual acuity and adverse effects. Results The median follow-up after initiating infliximab therapy was 19 months (range 12–29 months). At 12 months, eight of 14 patients (57%) had experienced no inflammatory attacks, and the frequency of attacks was significantly reduced when compared with the 6-month period just prior to infliximab use. Background retinal and disc vascular leakage assessed at 12 months improved in 11 of 14 patients (79%). Visual acuity improved or remained unchanged at 12 months in 26 of 28 eyes (93%). Infliximab therapy was terminated in two patients owing to infusion reactions. However, no serious adverse effects were observed. Conclusion Infliximab over the first year of treatment appeared effective in reducing ocular inflammatory attacks, as well as background retinal and disc vascular leakage, in patients with refractory uveoretinitis associated with Behcet9s disease.

Aim: The current study was designed to determine whether intravitreal injection of tacrolimus (FK506) modulates the gene expression of neurotrophic factor-related molecules in the retina from eyes with induced experimental autoimmune uveoretinitis (EAU) in rats. Methods: Rats were immunised with interphotoreceptor retinoid binding protein peptide (R14) and given intravitreal injection of tacrolimus on day 12 after immunisation. As control, immunised rats received intravitreal injection of vehicle. On day 15 after immunisation, changes in the genetic programme associated with neuroprotection and inflammatory responses in the retinas from both groups were determined by DNA microarray analyses and confirmed by real-time PCR analyses. Results: The gene expression of inflammatory responses was markedly reduced in tacrolimus-treated eyes. Genes for molecules associated with neuroprotection (oestrogen receptor, erythropoietin receptor, gamma-aminobutyric acid receptor, protein kinase C, glial cell line-derived neurotrophic factor receptor, fibroblast growth factor and neuropeptide Y receptor) were upregulated in the retinas from tacrolimus-treated eyes. Conclusions: Intravitreal injection of tacrolimus modulated the genes related to neuroprotection in the retina during the ongoing process of EAU. This treatment may be useful for the neuroprotection of retina with severe uveitis as well as for immunosuppression in the uveitic eyes.

Aim: To determine whether intravitreal injection of tacrolimus suppresses ongoing experimental autoimmune uveoretinitis (EAU) in rats. Methods: Rats were immunised with interphotoreceptor retinoid-binding protein peptide (R14) and given an intravitreal injection of tacrolimus on day 12 after immunisation. Intraocular inflammation was assessed by slit-lamp biomicroscopy and histopathological examination. Interferon γ and tumour necrosis factor α protein levels in the ocular tissues were measured. Gene expression of chemokines was determined in ocular tissues by reverse transcription-polymerase chain reaction. To evaluate the systemic effect of intravitreal injection of tacrolimus, delayed-type hypersensitivity was measured by ear swelling. Results: Clinical and pathological scores showed that ocular inflammation of tacrolimus-treated eyes was markedly less than that of vehicle-treated eyes. The amount of interferon γ and tumour necrosis factor α was considerably inhibited in tacrolimus-treated eyes. The gene expression of monocyte chemattractant protein-1 (MCP-1) and regulated upon activation, normal T cell expressed and secreted (RANTES) was markedly reduced in tacrolimus-treated eyes. Delayed-type hypersensitivity responses were not impaired in tacrolimus-treated rats. Conclusions: Intravitreal injection of tacrolimus was highly effective in suppressing the ongoing process of EAU without any side effects on systemic cellular immunity. This treatment may be useful in the management of patients with severe uveitis.

Aims: In early S-antigen induced experimental uveitis (EAU), photoreceptor mitochondrial proteins are nitrated prior to macrophage infiltration of the retina, suggesting that oxidative stress is an initial event in the development of EAU. We attempted to detect the oxidative stress and localise it in the EAU retina. Methods: Lewis rats were immunised with S-antigen in complete Freund’s adjuvant (CFA). Animals were injected with CFA alone and non-immunised animals served as controls. Immunised and non-immunised animals were killed on day 5 and subsequent days. Isolated retinas were processed for inducible nitric oxide synthase (iNOS), tumour necrosis factor (TNF)α, interferon (IFN)γ, interleukin (IL)Iα and CD28 expression by real time polymerase chain reaction. In addition, iNOS was colocalised with cytochrome c oxidase on day 5 of EAU. Oxidative stress was detected by 2′, 7′-dichlorodihydrofluorescein diacetate and localised by a mitochondrial specific marker. Leucocyte and T cell infiltration in the retina/choroid was evaluated by immunohistochemistry. Results: The iNOS, TNFα, IFNγ, IL1α and CD28 transcripts were significantly upregulated on day 5 in EAU, and iNOS was colocalised with cytochrome c oxidase in the photoreceptor mitochondria. Oxidative stress was seen primarily in the photoreceptor mitochondria. Occasional T cells were present in the retina at this stage. Conclusions: During early EAU, mitochondrial oxidative stress is selectively noted in the photoreceptor inner segments. The oxidative stress appears to result from iNOS upregulation in the photoreceptor mitochondria and cytokine generation in the retina by a few antigen specific infiltrating T cells.

Microbial agents have an important role in the pathogenesis of various inflammatory eye diseases, such as uveitis and keratitis. Microbial infections of the eye such as microbial keratitis, ocular onchocerciasis, bacterial endophthalmitis, viral retinitis, and other infectious uveitis are unfortunately common. In addition, microbial agents have been implicated in the pathogenesis of “non‐infectious” immune mediated diseases such as HLA‐B27 associated acute anterior uveitis. Toll‐like receptors (TLR) are a family of pattern recognition receptors that initiates rapid host innate immune response to microbial components known as pathogen associated molecular patterns, which are unique to a given class of microbes, such as lipopolysaccharide of Gram negative bacteria. Recent in vitro and in vivo studies have demonstrated the expression and function of TLRs in the eye, with significant implications for better understanding of ocular immunity and the pathogenesis of inflammatory eye diseases affecting the cornea, uvea, and retina.

Aim: To investigate whether retinal changes in children with severe malaria affect visual acuity 1 month after systemic recovery. Methods: All children with severe malaria admitted to a research ward in Malawi during one malaria season were examined by direct and indirect ophthalmoscopy. Visual acuity was tested in those attending follow up by Cardiff cards, Sheridan-Gardiner single letters, or Snellen chart. Results: 96 (68%) children attended follow up, of whom 83 (86%) had visual acuity measured. Cardiff cards were used in 47 (57%) children, and Sheridan-Gardiner letters or Snellen chart in 29 (35%). There was no significant difference in the mean logMAR visual acuity between groups with or without macular whitening (0.14 versus 0.16, p = 0.55). There was no trend for worse visual acuity with increasing severity of macular whitening (p = 0.52) including patients in whom the fovea was involved (p = 0.32). Six (4.2%) children had cortical blindness after cerebral malaria, and all six had other neurological sequelae. Ophthalmoscopy during the acute illness revealed no abnormalities in four of these children. Conclusion: Retinal changes in severe malaria, in particular macular whitening, do not appear to affect visual acuity at 1 month. This supports the hypothesis that retinal whitening is due to reversible intracellular oedema in response to relative hypoxia, caused by sequestered erythrocytes infected by Plasmodium falciparum . Impaired visual functioning after cerebral malaria is not attributable to retinal changes and appears to be a cortical phenomenon.

Aim: To evaluate the diagnostic value of polymerase chain reaction (PCR) performed on aqueous humour for the detection of viral DNA in patients with necrotising herpetic retinitis. Methods: The clinical features and laboratory results of 22 patients (29 eyes) presenting with necrotising herpetic retinitis between March 1999 and June 2001 were reviewed retrospectively. Aqueous humour was obtained after anterior chamber paracentesis and PCR was performed in all cases. Results: Viral DNA was detected in the aqueous humour of 19 patients (86.4%). Epstein-Barr virus (EBV) seroconversion was evidenced in one additional patient. In the acute retinal necrosis (ARN) group (n = 19), varicella zoster virus (VZV) DNA was identified in six patients, herpes simplex virus 1 (HSV-1) DNA in two patients, herpes simplex virus 2 (HSV-2) DNA in four patients, and cytomegalovirus (CMV) genome in four patients. In the progressive outer retinal necrosis (PORN) group (n = 3), VZV DNA was detected in all patients. No sample was positive for more than one virus. Conclusions: PCR analysis of aqueous humour in patients with clinical features of necrotising viral retinitis can provide specific aetiological orientation and the method appears to be safe and highly sensitive.

Aim—To assess the impact of highly active antiretroviral therapy (HAART) on the prevalence and progression of CMV retinitis (CMVR) among AIDS patients with baseline CD4 cell counts

To determine the prevalence of cytomegalovirus virus (CMV) retinopathy among a consecutive group of Tanzanians with AIDS with CD4 count100 cells/μl.Patients with HIV infection with CD4 count100 cells/μl presenting consecutively to infectious disease services at two hospitals were examined by indirect ophthalmoscopy with fully dilated pupils. Additional clinical information was collected by interview and from patient files.One-hundred and fifty patients with CD4 count100 cells/μl were examined, of whom 74 had CD4 count50 cells/μl; 129 patients (86%) were classified as WHO stage 3 or 4. Only two patients (1.3%; 95% CI 0 to 2.3%) had CMV retinitis.This study demonstrates that AIDS patients in Tanzania do survive into the stage of severe immunosuppression, and that even among this group CMV retinitis is very uncommon. This supports previous studies reporting low prevalence of CMV where CD4 counts were not available. Differences in immune response in AIDS patients in different settings may depend on environmental exposure to specific viruses early in life.

A 19 year-old Caucasian female was referred with a 3-month history of unilateral, progressively worsening vision accompanied by flashes and floaters. She denied any associated pain on eye movements, headaches or preceding flu-like symptoms. Her vision was documented 20/25 in both eyes, with a mild myopic astigmatism during a routine eye exam 6 months prior to the onset of symptoms. She had no significant medical history except three syncopal episodes over the prior 2 years. The patient, who was living in the northeast of the USA (Connecticut), denied any history of travel other than a trip to California one …

Over the past 20 years, drug development has led to numerous medications with the potential to treat intraocular disease. These medications usually require systemic or frequent topical administration, which can limit the types of medications that can be used and the diseases that can be treated effectively. Topical administration of medications can successfully treat a number of ocular diseases such as glaucoma, inflammation of the anterior segment or ocular surface, and external diseases of the eye. Nevertheless, topical delivery often fails to provide therapeutic levels in the vitreous cavity or posterior segment, and therefore is inadequate in the treatment of vitreoretinal diseases. Drugs can often be delivered to the posterior segment by injection via the pars plana, as is the case, for example, with ganciclovir, foscarnet, and cidofovir. However, depending on the rate of clearance from the vitreous of a particular medication, large boluses and frequent administrations may be required to ensure therapeutic levels over an extended period of time. Frequent injections in clinical practice may not be practical for chronic diseases that can sometimes require multiple weekly administrations over months or years. In addition, multiple intraocular injections can lead to an increased likelihood of complications, such as vitreous haemorrhage, retinal detachment, and endophthalmitis. The blood-ocular barrier is the main obstacle in the treatment of intraocular disease with systemic medications. Poor penetration of many drugs into the eye not only limits the number of medications available for the treatment of ocular diseases, but also limits the extent to which those available can be used without incurring serious systemic side effects. Medications, such as prednisone, cytotoxic agents for the treatment of intraocular inflammation, and antivirals for the treatment of cytomegalovirus (CMV) retinitis often cause severe side effects at the dosages needed to achieve their desired therapeutic effect. This is particularly problematic …

AIMS To report a series of patients requiring treatment for falling visual acuity associated with immune recovery vitritis, a recently described syndrome of a predominantly vitreous inflammatory reaction in patients with AIDS and cytomegalovirus (CMV) retinitis. METHODS The medical records of all patients requiring treatment for falling visual acuity associated with immune recovery vitritis were reviewed between March 1996 and March 1998. RESULTS Nine eyes in seven patients required treatment for falling visual acuity. All patients had inactive CMV retinitis and had received highly active antiretroviral treatment including a protease inhibitor. Vitreous inflammation developed at a mean of 5.5 months (range 1–14) after starting a protease inhibitor. The onset of inflammation correlated with a mean rise in CD4 + lymphocyte levels of 83 × 10 6 /l (range 30–128). The visual acuity fell by a mean of 2.8 Snellen lines (range 1–4) before treatment, and rose by a mean of 1.9 Snellen lines (range 0–4) after treatment with orbital floor steroids. The mean time interval between treatment with orbital floor steroids and improvement in visual acuity was 3.5 weeks (range 1–8). Following treatment the visual acuity improved or remained stable in all nine eyes, eight eyes returning to within one line of their preinflammation Snellen visual acuity. No eyes developed reactivation or progression of CMV retinitis after treatment, and none developed any other pathology. CONCLUSIONS Orbital floor steroids appear to be have a useful role in the treatment of persistent immune recovery vitritis where the visual acuity is compromised.

BACKGROUND/AIM—Nasal administration of retinal antigens induces systemic tolerance which results in suppression of experimental autoimmune uveoretinitis (EAU) when subsequently exposed to antigen. The aim was to establish if tolerance induction alters retinal infiltrating leucocyte phenotype and cytokine profile in tolerised animals when there is significantly reduced tissue destruction despite immunisation with retinal antigen. METHODS—Female Lewis rats were tolerised by intranasal administration with retinal extract (RE) before immunisation with RE to induce EAU. Control animals were administered phosphate buffered saline (PBS) intranasally. Post immunisation, daily clinical responses were recorded and at the height of disease, retinas were removed and either infiltrating leucocytes isolated for flow cytometric phenotype assessment and intracellular cytokine production, or chorioretina processed for immunohistochemistry. Fellow eyes were assessed for cytokine mRNA by semiquantitative RT-PCR. RESULTS—Flow cytometric analysis showed that before clinical onset of EAU there is no evidence of macrophage infiltration and no significant difference in circulating T cell populations within the retina. By day 14 a reduced retinal infiltrate in tolerised animals was observed and in particular a reduction in numbers of "activated" (with respect to CD4 and MHC class II expression) macrophages. Immunohistochemistry confirmed these findings and additionally minimal rod outer segment destruction was observed histologically. Cytokine analysis revealed that both IL-10 mRNA and intracellular IL-10 production was increased in tolerised eyes 7 days post immunisation. Although by day 14 post immunisation, IL-10 production was equivalent in both groups, a reduced percentage of IFN-γ+ macrophages and IFN-γ+ CD4+ T cells with increased percentage of IL-4+ CD4+ T cells were observed in tolerised animals. CONCLUSIONS—Leucocytic infiltrate is not only reduced in number but its distinct phenotype compared with controls implies a reduced activation status of infiltrating monocytes to accompany increased IL-10 and reduced IFN-γ production in tolerised animals. This modulation may in turn contribute towards protection against target organ destruction in EAU. Keywords: intranasal tolerance; experimental autoimmune uveoretinitis; retina; cytokines; flow cytometry

Background: HIV has various ocular manifestations and with the widespread introduction of highly active antiretroviral therapy (HAART), their pattern and prevalence is expected to change. Therefore, we evaluated the HIV/AIDS patients on HAART for ocular manifestations and blindness. Methods: In this cross-sectional study, 112 HIV-positive patients on HAART presenting to the HIV clinic with CD4 count ⩽200 cells/µl were enrolled. The WHO clinical stage, CD4 count, duration of HIV and HAART were recorded. An ocular examination was conducted, and the prevalence of ocular manifestations and blindness was determined. Results: The prevalence of ocular manifestations in HIV/AIDS patients on HAART was 8% (nine out of 112). Seven (6%) of the patients had visual impairment including one patient with blindness. The ocular manifestations included HIV retinopathy (5%), immune recovery uveitis (3%), immune recovery vitritis (3%) and Cytomegalovirus retinitis (2%). The prevalence of ocular manifestations and visual impairment was higher with the CD4 count of 0–100 cells/µl (p = 0.002). The prevalence of ocular manifestations was also higher in patients with WHO clinical stages 3 and 4 (p = 0.017). Conclusions: HAART may be the cause for decline in the prevalence of ocular diseases and visual impairment in HIV/AIDS patients. CD4 count and WHO clinical stage may help predict their occurrence.

BACKGROUND/AIMS—Toxoplasma retinochoroiditis (TR) is an important cause of blindness and visual morbidity, affecting young adults. It has been postulated that some of the retinal damage observed in TR is due to antiretinal autoimmune mechanisms. METHODS—Humoral antiretinal autoimmunity in TR was investigated by indirect immunofluorescence (IIF) on normal human cadaveric retina and by a human retinal S-antigen ELISA. 36 patients with TR were separated on clinical grounds into those with first recurrence of disease (n=18) or those with multiple recurrences (n=18). Patients were also segregated into those with active (n=28) or quiescent disease (n=8). Serum from 16 normal controls (six with positive toxoplasma serology and 10 without) with no evidence of eye disease and 12 patients with idiopathic retinal vasculitis (IRV) were also tested. RESULTS—Sera from 34 of the 36 patients (94%) with TR demonstrated photoreceptor layer reactivity by IIF contrasting with six of 16 normal controls (p= 0.05). Antiretinal autoantibody as detected by IIF did not run in parallel with S-antigen reactivity. CONCLUSIONS—The data indicate that the extent of antiretinal reactivity within TR is not accounted for by anti-S-antigen antibodies alone. This remarkably high prevalence of antiphotoreceptor antibody in TR as opposed to that found in either healthy or disease controls suggest that these antibodies may be co-pathogenic in toxoplasma retinochoroiditis. Keywords: retinochoroiditis; toxoplasma; immunofluorescence; autoimmunity

Aim: To discuss the rationale for different techniques of treatment for DUSN (diffuse unilateral subacute neuroretinitis) and their effectiveness in two patients from south India. Methods: Two rare cases of live worms in DUSN from India are reported, where filarial Brugia malayi is endemic. Both cases presented with progressive unilateral loss of vision with no history of animal contact. They were 40 year old, apparently healthy men. In case 1, the worm (1500–2000 μm) was easy to identify with wriggling movements among crisscrossing diffuse subretinal tracks. The worm was destroyed by a single shot of laser to its advancing end, which was followed by oral steroid to control the inflammation caused by the dead worm. In case 2, the worm was small and difficult to identify. Initially diffuse neuroretinitis was diagnosed and treated with intravenous methylprednisolone and oral corticosteroid. A week later, a small live worm (400–600 µm) was found and subsequently destroyed by laser photocoagulation followed by a combination of anthelminthics. Results: The patients’ vision had improved to 6/60–6/36 from counting fingers after a few weeks. Conclusion: The role of a combination of laser treatment, systemic steroid, and anthelminthics is discussed.

AIM: To determine the value of the polymerase chain reaction (PCR) technique and the analysis of intraocularly produced antibodies by calculating a Goldmann-Witmer quotient (GWq) as diagnostic assays in the confirmation of a clinically diagnosed cytomegalovirus (CMV) retinitis in a group of unselected AIDS patients. METHODS: Eleven samples of undiluted ocular fluid, obtained from nine AIDS patients with a clinically diagnosed CMV retinitis were analysed for the presence of genomic DNA from CMV, HSV-1, VZV, and EBV by PCR. Nine of these samples were analysed for the presence of locally produced IgG antibodies against these herpesviruses by calculating a GWq. Ten samples obtained from patients with various entities of clinical non-herpetic uveitis and 17 samples of aqueous humour obtained at cataract surgery were used as controls. RESULTS: In 10 out of 11 samples from AIDS patients (91%) the presence of CMV DNA was demonstrated. In four out of nine (44%) patients this was accompanied by CMV DNA in the blood indicating a CMV viraemia. In one sample, VZV DNA was detected and in another sample both CMV and VZV DNA were detected. No HSV-1 or EBV DNA could be demonstrated in these 11 samples. In contrast, simultaneous analysis of locally produced IgG antibodies against herpesviruses could not confirm the initial diagnosis of CMV retinitis. Ocular fluid samples obtained from 10 control uveitis patients were negative for DNA from CMV, VZV, and EBV by PCR. In one of 10 uveitis control samples HSV-1 DNA was detected; antibody analysis did not confirm this. In the uveitis control group, a significant GWq was calculated in one sample for HSV-1 and in another sample for VZV. The cataract control samples were all herpesvirus DNA negative by PCR. CONCLUSIONS: To establish the diagnosis of CMV retinitis in AIDS patients, ophthalmoscopic examination is a sensitive method. In confirming a diagnosis in indistinctive cases, application of a PCR assay detecting CMV DNA is a more sensitive method than analysis of locally produced antibodies by calculating a GWq. In clinical non-herpetic uveitis, secondary release of HSV-1 and VZV should be considered requiring additional therapeutic anticipation.

BACKGROUND--The prolongation of survival of patients with herpesvirus retinitis and AIDS has been associated with a rise in the incidence of retinal detachment. In such cases, however, retinal reattachment may be difficult to achieve, and postoperative visual acuity may be poor despite anatomically successful surgery. METHODS--In order to examine factors affecting the visual outcome of surgery, a retrospective review of 29 patients with retinal detachment, herpesvirus retinitis, and AIDS was performed. Retinal reattachment surgery (32 procedures) or prophylactic laser demarcation (five procedures) was performed in 28 eyes of 23 patients. RESULTS--The macula was attached in 23/28 (82%) eyes at the last outpatient visit. Best postoperative visual acuity (median 6/18, range 6/6-hand movements) was significantly greater than final postoperative acuity (median counting fingers, range 6/6-no perception of light) (Wilcoxon sign rank test, p = 0.003), and was retained for a median of 3 months (1-91 weeks) after surgery. Poor visual outcome as evidenced by submedian final visual acuity was invariably associated with persistence of macular detachment, and significantly associated with the occurrence of optic atrophy (odds ratio = 5, p = 0.02). CONCLUSION--Retinal reattachment surgery appears justified in patients with herpesvirus retinitis and AIDS, but postoperative visual deterioration may occur in association with optic atrophy.

Background: Healed cytomegalovirus (CMV) retinitis in the setting of highly active antiretroviral therapy (HAART) is complicated by inflammatory sequelae and vision loss. Aim: To determine the long term visual outcome of AIDS patients with CMV retinitis who received HAART. Methods: 90 eyes of 63 consecutive AIDS patients with extramacular CMV retinitis were studied prospectively. Results: Immune recovery status was related to time to onset of epiretinal membrane (p=0.05) and cystoid macular oedema (p=0.06) as well as to the incidence of cataract (p=0.001) and moderate vision loss (p

The aim of this study was to investigate the T lymphocyte subsets involved in experimental autoimmune uveoretinitis (EAU) by quantifying the numbers of cells expressing mRNA for each of the lymphokines interferon gamma, interleukin 2, interleukin 4, and lymphotoxin throughout the disease process. Lewis rats were immunised with retinal S-antigen to provide a model of inflammatory eye disease. In situ hybridisation using cDNA probes specific for interferon gamma, IL2, IL4, and lymphotoxin mRNA were utilised to localise lymphokine mRNA expression by infiltrating cells and the numbers of positive cells counted. Localisation of mRNA for all four probes was found on increasing cell numbers as the disease process progressed. Similar numbers of cells expressed mRNA for each lymphokine, generally a small percentage of the T lymphocyte total. Activated cells within the eye express mRNA for interferon gamma, IL2, IL4, and lymphotoxin in EAU suggesting a mixed population of T lymphocyte subsets.

To study its safety and efficacy in treating cytomegalovirus (CMV) retinitis, an AIDS patient received an intravitreal injection of liposome encapsulated ganciclovir in the right eye. The left eye served as a control, receiving intravitreal free ganciclovir. The right eye showed no retinal haemorrhages or detachment; however, vision declined initially, stabilising later. Weekly examination showed neither progression of the CMV retinitis nor new lesions in the right eye. The left eye showed reactivation of old CMV retinitis. Liposome encapsulated ganciclovir reduced the number of intravitreal injections, stabilising CMV retinitis, and warrants further study.

The efficacy and tolerance of high dose intravitreal foscarnet for cytomegalovirus retinitis in patients with AIDS was studied. Foscarnet in a dose of 2400 micrograms was injected directly into the vitreous of 11 patients (15 eyes). Five patients had active retinitis (eight eyes, 53.3%), and received a 3 week induction therapy of six injections as the first step. Six patients had initial inactive retinitis (seven eyes, 46.7%), and received only maintenance therapy which consisted of a weekly injection. The main indications for intravitreal therapy were: myelosuppression, kidney toxicity, catheter related sepsis, or refusal of intravenous therapy. The patients were followed for a mean period of 16 weeks (range 8-28 weeks) and received a total of 304 injections. Vitreous foscarnet levels were measured by high performance liquid chromatography. After a 3 week course of induction therapy, complete resolution of the active retinitis was seen in 62.5% (5/8 cases), while 37.5% (3/8 cases) had partial resolution. No cases failed to respond or progress. The rate of relapse on maintenance therapy was 33% (five of 15 eyes) by 20 weeks, and two of these eyes did not respond to reinduction and progressed in involvement of the macula or optic nerve. Neither important local complications nor intraocular drug toxicity were observed. Vitreous foscarnet levels in two different patients were 896 mumol/l and 74.9 mumol/l at 22 3/4 hours and 42 1/2 hours after the injection. Intravitreal foscarnet appears to be a safe, effective, and useful alternative in patients with intolerance to intravenous and viral therapy.

Current immunotherapy of posterior uveitis is non-specific and limited by drug toxicity and unpredictable relapses on therapy. Alternative modes of therapy being investigated using the rat model of experimental autoimmune uveoretinitis (EAU) have included the induction of tolerance with oral administration of milligram quantities of retinal antigens. In this preliminary report we demonstrate that tolerance to retinal antigens can be induced via the upper respiratory tract with microgram doses of antigen, preventing subsequent induction of EAU.

S-antigen induced experimental autoimmune uveoretinitis (EAU) was produced in the Royal College of Surgeons (RCS) strain of rat which develops a photoreceptor dystrophy within 2 weeks of birth. Animals were sensitised at 60, 90, and 105 days of age: all animals developed disease, but onset was significantly delayed in older (105 day) animals compared with those aged 60 days at sensitisation (p 0.003). Disease was characterised by the early development of complete serous retinal detachment which resolved in a few days: the prevalence of retinal detachment was increased to 80% in dystrophic animals compared with 10% in the congenic, non-dystrophic controls (p < 0.001). Anterior uveitis was seen in 17/30 control strain eyes, but in none of 30 dystrophic eyes (p < 0.001). Genetically determined photoreceptor and retinal pigment epithelium dysfunction in the RCS rat, which may involve the local accumulation of altered S-antigen, predisposes the dystrophic strain to display an acute retinal detachment in the early stages of EAU. This phenomenon illustrates how biochemical dysfunction of a target organ may influence susceptibility, form, and severity of an experimental autoimmune disease.

Cataracts often occur in humans secondary to uveitis. Uveitis may be caused by various infectious agents, but rarely is the agent detected in the cataract. Mycoplasma-like organisms (MLO) were recently reported to cause human uveitis and retinitis. Cataracts were often present in those inflamed eyes. MLO are intracellular cell wall deficient pathogenic bacteria. They are pleomorphic tubulospherical and filamentous organisms with a characteristic ultrastructural appearance. No MLO culture system has been found despite 20 years of effort. The diagnosis of MLO disease rests on detection of the organisms in parasitised cells by a transmission electron microscope and response to antibiotics. In human intraocular inflammatory disease MLO are detectable in parasitised leucocytes and retinal pigment epithelial cells at the disease sites. Inoculation of MLO from a human source into mouse eyelids produced intraocular, chronic, progressive, inflammatory disease, with intraocular leucocytes parasitised by MLO in 15 of 100 mice versus 0 in 200 controls (p less than 0.05). This report describes the cataracts with MLO-parasitised intralenticular leucocytes in the inflamed eyes of 14 of those 15 mice versus 0 in 200 control mice (p less than 0.05). The results indicate that MLO penetrated the lens capsules to produce the cataracts, and they suggest that MLO could cause human cataracts. Alternative methods for detection of MLO and rifampin treatment of MLO intraocular disease are discussed.

AIM—To describe the risk of developing cytomegalovirus (CMV) retinitis after a first episode of extraocular CMV disease in AIDS patients. METHODS—A review of the clinical records of 20 AIDS patients, without CMV retinitis, with histologically confirmed extraocular CMV disease, was performed. The main outcome measures were occurrence of CMV retinitis, time to development of CMV retinitis, relation to maintenance therapy, and survival. RESULTS—A CMV retinitis was diagnosed in 17 of 20 (85%) patients with an immunohistologically confirmed diagnosis of extraocular CMV disease after a mean follow up of 6.4 months. Four patients received maintenance therapy. Three of them developed retinitis after a mean of 9.6 months (range 2-16 months). Sixteen did not receive maintenance and retinitis was diagnosed in 14 of them after a mean of 5.7 months (range 2-11 months). Mean survival was 9.9 months after the diagnosis of extraocular disease, and 4.5 months after the diagnosis of retinitis. In the four patients receiving maintenance therapy, mean survival was 11.5 months, and in the 16 other patients mean survival was 9.5 months. Patients did not receive protease inhibitors. CONCLUSION—In the preprotease inhibitor era extraocular CMV disease strongly predisposes to the subsequent development of CMV retinitis. Although maintenance therapy did not prevent the occurrence of retinitis, the time period between both events seems to lengthen considerably. In patients receiving maintenance survival is also longer. Keywords: cytomegalovirus retinitis; risk factor; extraocular CMV disease; maintenance therapy

AIM—To gain insight into the course of CMV retinitis (CMVR) in AIDS patients receiving protease inhibitors (PI), and to evaluate whether certain patterns of CD4 response are indicative of the clinical outcome and the risk of recurrence. METHODS—15 consecutive AIDS patients receiving maintenance therapy for CMVR were included in a prospective observational cohort study at the university hospital between July and October 1996. Patients were evaluated for signs of CMVR activity and intraocular inflammation. CMVR recurrence was defined as the primary clinical endpoint. Follow up was performed until July 1997. No patient was lost to follow up. Clinical outcome was related to CD4+ lymphocyte counts, which were monitored every 6 weeks. Highly active antiretroviral treatment regimen including PI was started at study entry. RESULTS—All recurrences (n=7) were in patients who failed to have a sustained increase in CD4 counts, whereas CMVR remained inactive during a follow up of 42-52 weeks in those who were able permanently to restore their CD4 values to 100×106/l or more (n=5). The remaining three patients died after 12, 16, and 50 weeks, respectively, without recurrences. All relapses of CMVR were seen after 6-16 weeks, and at CD4 counts well below 100×106/l. CONCLUSIONS—The beneficial effects of PI treatment correlate with the pattern of CD4 response. Sustained increases in CD4 counts achieved in the first 16 weeks of treatment are associated with a prolonged period of CMVR quiescence. Poor initial response is associated with a high risk of CMVR recurrence. Keywords: AIDS; cytomegalovirus retinitis; HAART; protease inhibitors

BACKGROUND: Although intravitreal high dose ganciclovir has previously been found to provide excellent control of cytomegalovirus (CMV) retinitis, little was known about the vitreous concentrations of ganciclovir after a 2 mg intravitreal injection. METHODS: Eleven vitreous samples were taken from seven patients with CMV retinitis at 24 and 72 hours after a 2 mg intravitreal injection of ganciclovir and the concentration of ganciclovir was measured by high performance liquid chromatography. RESULTS: The mean concentration of ganciclovir at 24 hours was 143.8 mg/l (95% confidence interval 97.8-190) and at 72 hours was 23.4 mg/l (95% CI 0-49.7). The half life ranged from 11.9 to 26.3 (mean 18.8) hours in the four patients who had two samples taken. The mean half life calculated from the mean concentrations at 24 and 72 hours was 18.3 hours, so the calculated mean concentration at 7 days was 0.6 mg/l. CONCLUSIONS: This suggests that it takes about 7 days to eliminate the intravitreal ganciclovir, and that it is not likely to accumulate with weekly injections. The intravitreal concentrations achieved with high dose therapy remained above the ID50 for CMV (0.25-1.22 mg/l) for up to 7 days.

The purpose of this study was to determine the prevalence of retinal disease in a group of patients with AIDS in Malawi. Indirect ophthalmoscopy was performed on 99 patients with AIDS who were admitted consecutively to a medical ward at a central hospital. Necrotising retinitis was present in one eye of one patient examined. Non-infectious retinopathy was present in 13%. Retinitis is less common in AIDS patients from Africa compared with those from developed countries; it is believed that most patients die before acquiring it. Non-infectious retinopathy may also be less common.Retinal diseases and destructive eye pathology have been recognized in patients with HIV infections and acquired immunodeficiency syndrome (AIDS). Opportunistic viral agents such as herpes simplex virus, cytomegalovirus, and varicella zoster virus have also been described in severe cases of retinitis. Most of these studies have been carried out in developed countries. This article reports the findings of a Malawian study in which 99 AIDS patients (63 men and 36 women) were examined for retinal pathology. A diagnosis of AIDS required a positive enzyme-linked immunosorbent assay (ELISA). 58 patients (58.6%) had pulmonary tuberculosis (TB) and 10 others (10.1%) had extrapulmonary TB. Indirect ophthalmoscopy was performed on all patients. 73 patients (73.7%) had normal eye examinations; 1 patient (1.0%) was found to have necrotizing retinitis; only 13 patients (13.1%) showed noninfectious retinopathy. These studies suggest that retinitis is less common in sub-Saharan Africa than in developed countries. Tuberculosis was the most common opportunistic infection found in this study.

A 15-year-old girl developed retinitis pigmentosa-like fundus changes in the left eye and optic neuropathy in the right eye as well as cerebral demyelination as a result of late Lyme borreliosis (LB). The diagnosis was confirmed by polymerase chain reaction, which detected a Borrelia burgdorferi specific segment of a gene coding for 41 kD endoflagellin, both in the vitreous and the cerebrospinal fluid. The diagnosis was delayed because testing for Borrelia antibodies in serum and cerebrospinal fluid yielded negative results. However, later on, another laboratory reported the antibodies of the patient's pretreatment serum to be positive for LB.

Pantothenate kinase-associated neurodegeneration (PKAN; OMIM 234200) is caused by recessive mutations in PANK2 and is characterised by dystonia, cerebral iron accumulation, pathognomonic ‘eye of the tiger’ MRI finding, and pigmentary retinal degeneration.1 2 Bone spicule formation, retinal vessel attenuation and yellow-white globular deposits seen clinically have been correlated histopathologically with degeneration of photoreceptors, marked outer retinal layer thinning and accumulation of melanolipofuscin.2 In keeping with these observations, electroretinographic abnormalities, ranging from mild cone to severe rod–cone dysfunction, have been reported.3 Retinal telangiectasis, also known as Coats'-like or Coats'-type exudative vasculopathy, may occur in both syndromic and non-syndromic retinitis pigmentosa.4 However, we are not aware of previous published reports of exudative vasculopathy associated with PKAN. We have characterised a patient with a novel mutation in PANK2 that had spontaneous resolution of retinal telangiectasis. In October 2005, a 10-year-old girl was referred to Moorfields Eye Hospital …

We report our experience with the long-term management (13 years) of a patient with unilateral Posner–Schlossman syndrome (PSS), in whom cytomegalovirus (CMV) DNA was detected. Multiple treatment modalities were employed to control the number of relapses. Extensive retinal damage was observed even though clinically apparent retinitis was never observed during the follow-up period. A 48-year-old man had suffered from recurrent right hypertensive anterior uveitis since 1996 and was diagnosed with PSS on clinical grounds. The condition was controlled with intermittent topical corticosteroid and anti-glaucoma medications. A superior defect was documented in 2003 (figure 1) despite healthy optic discs with cup-to-disc ratio of 0.4 bilaterally. This was felt to result from intermittent high pressure spikes, despite intraocular pressure returning to normal between attacks. Figure 1 Humphrey's visual field from 2003, 2005, 2006 and 2009 showing progressive constrictive …

A 60-year-old Caucasian man presented with unilateral vitritis and retinitis. HIV was subsequently diagnosed, and the CD4+ count was high at 260 cells/μl. Serological, aqueous and vitreous testing for cytomegalovirus (CMV) and herpes viruses were normal. The patient was treated for presumed CMV retinitis with intravitreal ganciclovir and oral valganciclovir, but there was no response to therapy. After 6 months, the vitritis and retinitis persisted, and the CD4+ count remained at 210 cells/μL. Highly active antiretroviral therapy (HAART) was commenced, and the retinitis resolved over the following two months. The patient subsequently developed a homonymous hemianopic …

Ocular syphilis can present in many ways,1 especially in patients infected with HIV. The protean posterior segment manifestations include necrotising retinitis, retinal vascular occlusion, chorioretinitis, neuroretinitis and exudative retinal detachment.2 Nodular periarteritis, or Kyrieleis plaques, are a well-recognised finding in patients with toxoplasmic retinochoroiditis,3 but have only been reported in one previous case of syphilis. We describe the clinical presentation and treatment of an HIV-seropositive patient who developed Kyrieleis plaques in the setting of diffuse uveitis and syphilitic retinitis. A 48-year-old white man who had had HIV for 4 years presented with floaters and blurred vision of 3 weeks duration. The patient also reported evanescent skin …

We describe a real time polymerase chain reaction (PCR) technique for the detection of treponemal DNA in the vitreous of patients with suspected syphilitic uveitis. A 41 year old white homosexual male presented with a 1 week history of pain, redness, and reduced visual acuity in the right eye. There was a recent history of mouth ulcers and skin rashes involving the left lower limb. Corrected Snellen visual acuities were 6/60 and 6/6 in the right and left eyes respectively. In the right eye there were 4+ cells in the anterior chamber and vitreous. The right optic disc was swollen with patchy retinitis involving the inferior quadrants. The left eye was normal. Treponema specific serology tests, total antibody enzyme immunoassay assay (EIA) and Treponema pallidum particle agglutination test (TPPA) were strongly positive. Rapid plasma reagin (RPR) titre was 1:512, consistent with active treponemal infection. Subsequent cerebrospinal fluid analysis was also positive for both RPR and TPPA, …

The idiopathic retinal vasculitis, aneurysm, and neuroretinitis (IRVAN) syndrome is a rare clinical entity characterised by peripheral retinal vascular occlusion, retinal vasculitis, and multiple posterior retinal arterial aneurysms.1,2 In most reported cases, visual acuity was aggravated.2–4 We report a case of successfully treated IRVAN syndrome in which good long term visual acuity has been maintained. A 36 year old woman visited the Kansai Medical University Hospital on January 1999, complaining of flies flying in her right eye for the past year. She also had visual disturbance and metamorphopsia for 2 months in her right eye. Her best corrected visual acuity was 20/40 in the right eye and 20/16 in the left eye. Inflammatory cells …

In spite of lower viral loads and increasing T cell counts, AIDS patients receiving highly active antiretroviral therapy (HAART) are not always successful in mounting an immune response to some opportunistic pathogens. In fact, CMV retinitis, which was known to occur in HIV patients with CD4 counts below 50×106/l, has been described in immune reconstituted patients with CD4 counts above 200×106/l.1 It is therefore important to make observations about the clinical spectrum of infectious disease in immune reconstituted AIDS patients. Here we report an isolated lesion of molluscum contagiosum in …

Ocular toxoplasmosis may be remarkably atypical in situations of evident immunosuppression such as acquired immunodeficiency syndrome, malignancy, and use of chronic immunosuppressive drug therapy.1 Aggressive forms in immunocompetent hosts are very rare.2,3 We present a case of severe, bilateral necrotising retinitis by Toxoplasma gondii initially misdiagnosed as an acute retinal necrosis (ARN) syndrome, in a patient with systemic lupus erythematosus (SLE) and diabetes mellitus type 2, who was taking medium dose prednisone. A 47 year old woman reported a 3 month history of rapid visual loss in the right eye followed by a decrease in her left eye vision 2 months later. Twenty days before the onset of ocular symptoms the patient had a seizure. Her medical history showed a SLE,4 with an active lupus central nervous system disease controlled with prednisone (0.5 mg/kg/day), and type 2 diabetes mellitus. At her first visit to our service, visual acuity was hand movements in both eyes. Slit lamp examination showed 3+ aqueous cells and flare, and 2+ anterior vitreous cells in both eyes. The fundus showed a 2+ vitreous haze and almost 360° creamy white necrotising retinitis extending from the ora serrata to the posterior pole, including the macula in both eyes (Fig 1A and B). Thumbprint patches at the border between necrotic and scanty normal retina could be observed, and also diffuse vascular attenuation. Figure 1 (A) Fundus appearance of …

Coxsackievirus is a kind of enterovirus, which may cause respiratory and gastrointestinal symptoms, erythema, meningoencephalitis, myocarditis, pericarditis, and myositis. Although Coxsackievirus B4 is apparently a rare cause of chorioretinitis, Coxsackievirus infection and concurrent posterior segment inflammation have been disclosed in a few cases. However, iridocyclitis, scattered haemorrhagic dots, and occlusive retinal vasculitis have not previously reported as being features of Coxsackievirus B4 infectious ocular disease. A 34 year old man was referred to our hospital with a 2 week history of inferior visual field defect and visual loss in his right eye. His left eye was asymptomatic. A few days before the onset of visual manifestations, the patient noted a prodrome of viral infection, consisting of severe headache and high grade fever of 38.0–39.2°C, joint pain, and general malaise. There was no significant medical or family history. At the initial ophthalmic examination, his best corrected visual …

Cytomegalovirus (CMV) retinitis in children with congenital CMV infection is known to differ from that described in immunocompromised subjects, because it is present at birth and does not progress postnatally if the child is otherwise immunocompetent. Regarding treatment, there are limited data in infants with symptomatic congenital CMV infection and it is not known whether antiviral drugs alter the prognosis. We describe a case of congenital CMV retinitis that progressed postnatally and our treatment regimen. A 9 day old baby was referred to the eye clinic after having been diagnosed with congenital symptomatic CMV infection. During pregnancy, at 34 weeks, poor growth and ventriculomegaly were noted and a scan at 35 weeks showed bilateral cysts in the occipital horn of the lateral ventricles. He was born at 40 weeks by emergency caesarean section. The mother was a healthy 18 year old woman. His birth weight was 2.1 kg and his head circumference 31.5 cm, both of which were below the 0.4th centile. Brain magnetic resonance imaging confirmed the presence of bilateral occipital cysts and periventricular calcification. Serology and urine tests showed congenital CMV infection. The child had a normal immune system for his age. Eye examination revealed sheathing of the retinal vessels and haemorrhages, which involved the arcades and were more marked in the left eye (Fig 1A, B, C). Exudates were present in both eyes superior to the disc (Fig 1A). The following day the vasculitis in the left eye had progressed and was involving the macula. Treatment with ganciclovir 5 mg/kg/day intravenously was started in view of the active retinitis. One week after …

Cytomegalovirus (CMV) retinitis is the most common opportunistic ocular infection in patients with the acquired immune deficiency syndrome (AIDS).1 Before the advent of highly active antiretroviral therapy (HAART), CMV retinitis affected 30% of patients with AIDS at some time during the course of their disease.2 Cytomegalovirus retinitis is a late stage complication associated with low CD4+ T cell counts, typically less than 50 cells × 106/l.34 Cytomegalovirus retinitis was rare at CD4+ T cells >100 cells × 106/l.34 All of the available anti-CMV therapies suppress viral replication, but do not eliminate the virus. Unless immune reconstitution occurs, prolonged suppressive anti-CMV therapy (maintenance therapy) is required.15 Without immune reconstitution or maintenance therapy, CMV retinitis relapses within 3 weeks. As such, in the pre-HAART era, patients with CMV retinitis required lifetime maintenance anti-CMV therapy. HAART consists of combination therapy for the human immunodeficiency virus (HIV), with at least three drugs, typically two nucleoside reverse transcriptase inhibitors and either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor. HAART can result in marked suppression of HIV replication, improvement in immune function, increases in CD4+ T cells, decreases in opportunistic infections, and improved survival.6 With HAART, there has been a 55%–95% reduction in the number of new cases of the CMV retinitis, and the decrease varies depending upon the population being served.6-8 However, CMV retinitis continues to occur, albeit at a reduced incidence, and there …

Toxoplasmic retinochoroiditis (TRC) is an infectious disease caused by the protozoan Toxoplasma gondii . This infection affects many organs including the eyes. Most of the time ocular involvement occurs after a transplacental transmission, throughout pregnancy, but the infection can also be acquired. In immunocompetent patients, TRC is the most common cause of infection affecting the posterior segment. Clinically, the lesion appears as a white focal necrosis involving the full thickness of the retina, at the margin of an old pigmented chorioretinal scar. A vitreous inflammation is usually present and occasionally vasculitis is observed.1 We report the case of a healthy patient who developed a unilateral haemorrhagic retinochoroiditis (RC). The investigations performed were positive for a TRC. A 45 year old African man was referred with a 10 day history of a painless progressive visual loss affecting the left eye. No other ophthalmological or systemic complaints were present. His past medical history was unremarkable. Ophthalmological examination disclosed a vision of 20/20 in the right eye without correction and in the left …

Acute retinal necrosis (ARN) is a rare but serious ophthalmic manifestation of infection by the herpesvirus family. In the immunocompetent, the viral agent most frequently identified is varicella zoster (VZV) followed by herpes simplex (HSV-1 and HSV-2) and rarely cytomegalovirus and Epstein-Barr virus. The condition, which may present with synchronous or metachronous systemic or cerebral herpetic infection (encephalitis) is now recognised to occur at all ages,1 though VZV tends to affect the more elderly and herpes simplex the young. The majority of patients present with a short history of blurred vision, floaters, and mild ocular discomfort. In the immunocompetent, clinical examination reveals one or more well demarcated foci of retinal necrosis outside the major arterial arcades typically with a dense vitritis that may preclude a detailed view of the posterior segment. Disease progression is rapid with coalescence and posterior extension of areas of retinitis. Often there is an occlusive, sometimes haemorrhagic, vasculitis either adjacent to areas of retinitis or at the optic nerve. The visual prognosis for untreated cases is very poor.2 We report three immunocompetent patients with no evidence of concurrent herpesvirus infection in whom ipsilateral …

To assess the impact of highly active antiretroviral therapy (HAART) on the prevalence and progression of CMV retinitis (CMVR) among AIDS patients with baseline CD4 cell counts100 cells x 10(6)/l.A longitudinal cohort study of 1292 patients. CD4 cell counts and HIV viral load measurements were obtained before commencing therapy, at 3 months, 1 year, 2 years, and at last follow up. The CMVR prevalence rate was measured for the subgroup with baseline CD4 cell counts100 cells x 10(6)/l. CMVR adverse event (AE) rates per 100 person days at risk were calculated for the subgroup with CMVR and baseline CD4 cell counts100 cells x 10(6)/l.1292 patients were started on HAART. 8% of patients had CD4 counts50 cells x 10(6)/l and 40% had detectable HIV viral load at last follow up. The prevalence of CMVR for the subgroup with baseline CD4100 cells x 10(6)/l was 10%. For those with baseline CD4100 cells x 10(6)/l, the mean CMVR AE rate was greatest during the first 6 months of follow up after HAART commencement (p0.003). The mean AE rate per 100 person days at risk was 0.36 (95% CI 0.167 to 0.551) before starting HAART, and 0.14 (95% CI 0.085 to 0.199) after starting HAART (p = 0.03).HAART significantly prolongs the disease-free intervals in patients with pre-existing disease but recurrences persist within the first 6 months of starting therapy. AE were absent beyond 18 months of follow up in all patients including those with persistently low CD4 counts and detectable HIV viral load indicating clinical immunorestoration. New methods for monitoring the response to therapy are needed to identify those at risk.