Brian B. Berger

Ocular toxoplasmosis in patients with the acquired immunodeficiency syndrome

In seven of eight cases of presumed ocular toxoplasmosis in patients with AIDS, the diagnosis was supported by a reduction or resolution of intraocular inflammation and healing of necrotic retinal lesions after initiation of antiparasitic drug therapy including one or more of the following medications: pyrimethamine, sulfadiazine, clindamycin, tetracycline, or spiramycin. In two cases the diagnosis was confirmed histologically. The cases differed clinically and histopathologically from those in immunocompetent patients. There was no evidence that disease originated in preexisting retinochoroidal scars. Lesions frequently were bilateral and multifocal. Vitreous inflammatory reaction was a common clinical finding, but histopathologic examination demonstrated scant retinal inflammation in areas of necrosis. Ocular toxoplasmosis in these patients with AIDS probably resulted from newly acquired infection or dissemination of organisms from nonocular sites of disease. Infections became clinically inactive with drug therapy in all treated patients, but reactivation and progression of disease occurred when therapy was stopped in two of three patients. Severe retinal necrosis led to retinal tears or detachment in three cases. Ocular lesions were the first manifestation of Toxoplasma gondii infection in four of five patients with evidence of multisystem infection.

Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial

IMPORTANCE Panretinal photocoagulation (PRP) is the standard treatment for reducing severe visual loss from proliferative diabetic retinopathy. However, PRP can damage the retina, resulting in peripheral vision loss or worsening diabetic macular edema (DME). OBJECTIVE To evaluate the noninferiority of intravitreous ranibizumab compared with PRP for visual acuity outcomes in patients with proliferative diabetic retinopathy. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012 (mean age, 52 years; 44% female; 52% white). Both eyes were enrolled for 89 participants (1 eye to each study group), with a total of 394 study eyes. The final 2-year visit was completed in January 2015. INTERVENTIONS Individual eyes were randomly assigned to receive PRP treatment, completed in 1 to 3 visits (n = 203 eyes), or ranibizumab, 0.5 mg, by intravitreous injection at baseline and as frequently as every 4 weeks based on a structured re-treatment protocol (n = 191 eyes). Eyes in both treatment groups could receive ranibizumab for DME. MAIN OUTCOMES AND MEASURES The primary outcome was mean visual acuity change at 2 years (5-letter noninferiority margin; intention-to-treat analysis). Secondary outcomes included visual acuity area under the curve, peripheral visual field loss, vitrectomy, DME development, and retinal neovascularization. RESULTS Mean visual acuity letter improvement at 2 years was +2.8 in the ranibizumab group vs +0.2 in the PRP group (difference, +2.2; 95% CI, -0.5 to +5.0; P < .001 for noninferiority). The mean treatment group difference in visual acuity area under the curve over 2 years was +4.2 (95% CI, +3.0 to +5.4; P < .001). Mean peripheral visual field sensitivity loss was worse (-23 dB vs -422 dB; difference, 372 dB; 95% CI, 213-531 dB; P < .001), vitrectomy was more frequent (15% vs 4%; difference, 9%; 95% CI, 4%-15%; P < .001), and DME development was more frequent (28% vs 9%; difference, 19%; 95% CI, 10%-28%; P < .001) in the PRP group vs the ranibizumab group, respectively. Eyes without active or regressed neovascularization at 2 years were not significantly different (35% in the ranibizumab group vs 30% in the PRP group; difference, 3%; 95% CI, -7% to 12%; P = .58). One eye in the ranibizumab group developed endophthalmitis. No significant differences between groups in rates of major cardiovascular events were identified. CONCLUSIONS AND RELEVANCE Among eyes with proliferative diabetic retinopathy, treatment with ranibizumab resulted in visual acuity that was noninferior to (not worse than) PRP treatment at 2 years. Although longer-term follow-up is needed, ranibizumab may be a reasonable treatment alternative, at least through 2 years, for patients with proliferative diabetic retinopathy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01489189.

Vision-threatening Complications of Surgery for Full-thickness Macular Holes

OBJECTIVE To study complications of vitrectomy surgery for full-thickness macular holes. DESIGN A multicentered, randomized, controlled clinical trial. PARTICIPANTS Community and university-based ophthalmology clinics. INTERVENTION Standardized macular hole surgery versus observation. MAIN OUTCOME MEASURES Assessment of anatomic and visual outcomes and determination of postoperative complications at 12 months after randomization. RESULTS Posterior segment complications were noted in 39 eyes (41%). The incidence of retinal pigment epithelium (RPE) alteration and retinal detachment (RD) were 33% and 11%, respectively. One RD due to a giant retinal tear resulted in a visual acuity of light perception. Other complications included a reopening of the macular hole in 2 eyes (2%), cystoid macular edema in 1 eye (1%), a choroidal neovascular membrane in 1 eye (1%) and endophthalmitis in 1 eye (1%). Eyes with complications had significantly worse visual acuity outcomes as determined by the Early Treatment Diabetic Retinopathy Study, Word Reading, and Potential Acuity Meter charts (P < 0.01 for all comparisons). Eyes with macular holes greater than 475 microns were more than twice as likely to have complications than eyes with holes less than 475 microns (odds ratio [OR] = 2.2, P = 0.07). Before surgery, the stage of the hole was related to postoperative RPE changes (P < 0.0001) and the occurrence of postoperative RD (P = 0.0002). Intraoperative trauma was related to the occurrence of these complications (P < 0.0001 for RPE changes, P = 0.02 for RDs). Epiretinal membrane removal was related to RPE changes (P = 0.02) but not RDs. CONCLUSIONS The RPE alterations and RDs are common after macular hole surgery and result in significantly reduced postoperative visual acuity. The RPE changes may be related to surgical trauma or light toxicity. Further efforts to reduce complications associated with macular hole surgery are indicated.

Vitrectomy for Prevention of Macular Holes: Results of a Randomized Multicenter Clinical Trial

PURPOSE: The purpose of this study is to assess the benefit of vitreous surgery in preventing full-thickness macular holes in patients with impending (stage 1) macular holes. METHODS: A prospective randomized multicenter clinical trial was conducted on patients with full-thickness macular holes in their first eye (stage 3 or 4) and signs and symptoms of stage 1 macular holes in their fellow eye (study eye). The study eye was randomized to vitreous surgery or observation. Outcome was assessed by standardized measurement of visual acuity, detailed clinical examination, fundus photographs, and fluorescein angiography. RESULTS: A full-thickness macular hole developed in 10 (37%) of 27 patients in the vitrectomy group compared with 14 (40%) of 35 patients randomized to observation (P = 0.81). This difference of 3% has a 95% confidence interval of (-21%, 27%). CONCLUSION: The study was terminated because of low recruitment. The authors were unable to prove (or disprove) the benefit of vitreous surgery in patients with stage 1 macular holes. The authors can state, however, that should a beneficial effect from vitrectomy exist, it would probably be minimal. Considering the cost and morbidity of vitreous surgery, a conservative approach for stage 1 macular hole might be appropriate.Purpose: The purpose of this study is to assess the benefit of vitreous surgery in preventing full-thickness macular holes in patients with impending (stage 1) macular holes. Methods: A prospective randomized multicenter clinical trial was conducted on patients with full-thickness macular holes in their first eye (stage 3 or 4) and signs and symptoms of stage 1 macular holes in their fellow eye (study eye). The study eye was randomized to vitreous surgery or observation. Outcome was assessed by standardized measurement of visual acuity, detailed clinical examination, fundus photographs, and fluorescein angiography. Results: A full-thickness macular hole developed in 10 (37%) of 27 patients in the vitrectomy group compared with 14 (40%) of 35 patients randomized to observation ( P = 0.81). This difference of 3% has a 95% confidence interval of (-21%,27%). Conclusion: The study was terminated because of low recruitment. The authors were unable to prove (or disprove) the benefit of vitreous surgery in patients with stage 1 macular holes. The authors can state, however, that should a beneficial effect from vitrectomy exist, it would probably be minimal. Considering the cost and morbidity of vitreous surgery, a conservative approach for stage 1 macular hole might be appropriate.

Management of varicella zoster virus retinitis in AIDS

AIMS/BACKGROUND Varicella zoster virus retinitis (VZVR) in patients with AIDS, also called progressive outer retinal necrosis (PORN), is a necrotising viral retinitis which has resulted in blindness in most patients. The purposes of this study were to investigate the clinical course and visual outcome, and to determine if the choice of a systemic antiviral therapy affected the final visual outcome in patients with VZVR and AIDS. METHODS A review of the clinical records of 20 patients with VZVR from six centres was performed. Analysis of the clinical characteristics at presentation was performed. Kruskall–Wallis non-parametric one way analysis of variance (KWAOV) of the final visual acuities of patients treated with acyclovir, ganciclovir, foscarnet, or a combination of foscarnet and ganciclovir was carried out. RESULTS Median follow up was 6 months (range 1.3–26 months). On presentation, 14 of 20 patients (70%) had bilateral disease, and 75% (15 of 20 patients) had previous or concurrent extraocular manifestations of VZV infection. Median initial and final visual acuities were 20/40 and hand movements, respectively. Of 39 eyes involved, 19 eyes (49%) were no light perception at last follow up; 27 eyes (69%) developed rhegmatogenous retinal detachments. Patients treated with combination ganciclovir and foscarnet therapy or ganciclovir alone had significantly better final visual acuity than those treated with either acyclovir or foscarnet (KWAOV: p = 0.0051). CONCLUSIONS This study represents the second largest series, the longest follow up, and the first analysis of visual outcomes based on medical therapy for AIDS patients with VZVR. Aggressive medical treatment with appropriate systemic antivirals may improve long term visual outcome in patients with VZVR. Acyclovir appears to be relatively ineffective in treating this disease.

Retinal thickness in people with diabetes and minimal or no diabetic retinopathy: Heidelberg Spectralis optical coherence tomography.

PURPOSE To evaluate macular thickness in people with diabetes but minimal or no retinopathy using Heidelberg Spectralis optical coherence tomography (OCT). METHODS In a multicenter, cross-sectional study of mean retinal thickness, on Spectralis OCT in the nine standard OCT subfields, spanning a zone with 6-mm diameter, center point, and total retinal volume were evaluated. Central subfield (CSF) thickness was evaluated for association with demographic and clinical factors. Stratus OCT scans also were performed on each participant. RESULTS The analysis included 122 eyes (122 participants) with diabetes and no (n = 103) or minimal diabetic retinopathy (n = 19) and no macular retinal thickening on clinical exam. Average CSF thickness was 270 ± 24 μm. Central subfield thickness was significantly greater in males relative to females (mean 278 ± 23 μm vs. 262 ± 22 μm, P < 0.001). After adjusting for gender, no additional factors were found to be significantly associated with CSF thickness (P > 0.10). Mean Stratus OCT CSF thickness was 199 ± 24 μm. CONCLUSIONS Mean CSF thickness is approximately 70 μm thicker when measured with Heidelberg Spectralis OCT as compared with Stratus OCT among individuals with diabetes in the absence of retinopathy or with minimal nonproliferative retinopathy and a normal macular architecture. CSF thickness values ≥ 320 μm for males and 305 μm for females (~2 SDs above the average for this normative cohort) are proposed as gender-specific thickness levels to have reasonable certainty that diabetic macular edema involving the CSF is present using Spectralis measurements.

Prostatic carcinoma metastatic to choroid

Metastatic prostatic carcinoma of the choroid became clinically undetectable after orchidectomy and oestrogen administration. The choroidal tumour rapidly regressed over a 2-month period and clinically disappeared, with restoration of 6/6 vision from 6/60 and return of visual field. This dramatic response and lack of complications make hormonal manipulation the preferred mode of initial therapy in prostatic carcinoma metastatic to the choroid.

Bilateral Cytomegalovirus Panuveitis after High-Dose Corticosteroid Therapy

A 30-year-old previously healthy woman who recieved immunosuppressive doses of corticosteroids developed an unusual culture-proved cytomegalovirus panuveitis bilaterally. The atypical clinical course was marked by bilateral exudative detachements with minimal evidence of retinitis. Any patient receiving blood transfusions and immunosuppressive doses of corticosteroids is potentially at risk for developing ocular cytomegalovirus infection, and the clinical presentation of the ocular infection may be atypical.

Foveal Photocoagulation from Laser Iridotomy

Acute and permanent loss of vision has resulted from foveal photocoagulation during argon laser iridotomy. This complication can occur when the laser beam passes through the iridotomy nearly parallel to the visual axis. This is most likely to happen during enlargement of the iridotomy. A retinal burn of the macular region through a peripheral iridotomy was produced experimentally, and the mechanism of this complication is explained.

RANIBIZUMAB PLUS PROMPT OR DEFERRED LASER FOR DIABETIC MACULAR EDEMA IN EYES WITH VITRECTOMY BEFORE ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

Background: The approach to managing diabetic macular edema in eyes with previous vitrectomy is based on limited evidence. Therefore, an exploratory post hoc assessment of 3-year data from eyes with and without vitrectomy before randomization in a DRCR.net trial that evaluated ranibizumab + prompt or deferred laser for diabetic macular edema is presented. Methods: Visual acuity and optical coherence tomography outcomes were compared between eyes with and without previous vitrectomy. Results: At baseline, eyes with previous vitrectomy (n = 25) had longer duration of diabetes, worse visual acuity, less thickened central subfield measurements on optical coherence tomography and were more apt to have worse diabetic retinopathy severity level or previous treatment for macular edema or cataract surgery than eyes without a history of vitrectomy (n = 335). Analyses adjusted for these baseline imbalances did not identify substantial differences between eyes with and without previous vitrectomy at each annual visit through 3 years for the favorable visual acuity, optical coherence tomography central subfield thickness, or volume outcomes, although optical coherence tomography improvement appeared slower in vitrectomy eyes during the first year. Conclusion: This study provides little evidence that the beneficial clinical outcomes for patients with center-involved diabetic macular edema treated with anti-vascular endothelial growth factor are affected in the long term by previous vitrectomy.