Neovascular Glaucoma in MELAS syndrome.

Purpose: To describe examination and findings in a case of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) with particular focus on the ocular sequelae from diabetes. Observations: Neovascular glaucoma is not a common manifestation of MELAS. Conclusions and Importance: We present a rare case of neovascular glaucoma in a patient with MELAS with a history of diabetes, hearing loss, and macular dystrophy. MELAS should be suspected in patients with this constellation of symptoms.

Retinal Detachment and Epiretinal Membrane Development in Fellow-Eye Laser Prophylaxis.

Purpose: To determine the safety and efficacy of fellow-eye laser prophylaxis (FELP) in reducing the rate of retinal detachment (RD) in patients undergoing repair of a primary RD. Methods: Retrospective data were collected on the fellow eyes of consecutive patients undergoing primary RD repair. Patients lacking peripheral retinal pathology in the fellow eye or with less than 3 years of follow-up were excluded. Ninety-eight consecutive patients were identified who underwent FELP as compared with 28 who did not. No patient had symptoms in their fellow eye upon presentation. Rates of RD and epiretinal membrane (ERM) formation in the treatment group were compared with the control group. Results: Three of 98 (3.1%) patients developed RD despite having FELP compared with 5 of 28 (17.9%) in the control group (P = .005). In the FELP group, 16 (16.3%) patients developed ERM vs 7 of 28 (25.0%) in the group that did not receive prophylactic laser (P = .29). No patients in either the FELP or control group required surgery for ERM. Conclusions: Prophylactic laser to the fellow eye of patients undergoing primary RD repair reduced the risk of RD without significant risk of ERM formation.

Macular Findings of Patients on Pentosan Polysulfate Sodium.

INTRODUCTION: In 2018, a unique maculopathy associated with chronic pentosan polysulfate sodium (PPS) use for the treatment of interstitial cystitis (IC) was described, where the authors detailed macular retinal pigment epithelial abnormalities in six patients. In this paper, a retrospective study of a larger patient pool at one large tertiary retina practice was undertaken to evaluate patients taking PPS and their macular findings. MATERIALS AND METHODS: A retrospective chart review was performed on all patients presenting to a single large retina practice between 2011 and 2019. Patient's macular diagnosis, findings, optical coherence tomography scans, and macular auto-fluorescent scans were assessed. This project was Institutional Review Board (IRB) approved by the St Luke's Hospital IRB board (St Louis, MO, USA). RESULTS: Fifty-five patients were identified as taking PPS for IC. Fifty-three patients were found to have a diagnosis consistent with changes attributable to known macular diseases to include macular degeneration and pattern dystrophies. Two (4%) of fifty-five patients had macular findings suggestive of PPS toxicity. The first was a 58-year-old female with subtle retinal pigment epithelium (RPE) deposits on optical coherence tomography that exhibited hyper-autofluorescence. The second was a 72-year-old female with 14 years of PPS use who exhibited RPE excrescences and parafoveal areas of atrophy. CONCLUSIONS: Pentosan polysulfate sodium may be the cause of macular findings in a small percentage of patients referred to a tertiary retina practice. Although causation of macular changes with PPS use has yet to be elucidated, clinicians should be aware of this possibility when assessing patients with atypical macular findings. Future longitudinal studies are necessary to evaluate a definitive relationship. This paper should remind all clinicians of the importance of a throughout review of the patient's medication list as novel toxicities may become apparent years after initial FDA trials. The strength of this study is the larger patient population compared to earlier studies, and the main weaknesses include the retrospective nature of the study, lack of family and genetic testing, and lack of multimodal imaging for all patients.

Characterization and diagnosis of retinoschisis and schisis detachments using spectral domain optical coherence tomography.

PURPOSE: To characterize retinoschisis in a large series using spectral domain optical coherence tomography (SD-OCT), including rates of schisis detachment and macular involvement in cases of peripheral retinoschisis. METHODS: In this retrospective, cross-sectional, descriptive study, consecutive patients with diagnosis of retinoschisis in at least one eye were identified using billing codes between January 2012 and May 2021. Charts were reviewed to verify diagnosis of retinoschisis or schisis detachment. SD-OCT and clinical examination was used to identify frequency of macular schisis, peripheral schisis, and schisis detachment, and characteristics of retinoschisis including frequency of inner and outer wall breaks, distribution of layers split, and location of involvement of peripheral pathology. SD-OCT images of insufficient quality were excluded from the pertinent analysis. RESULTS: 281 eyes of 191 patients were included. 195 (69.4%) eyes had peripheral retinoschisis, 15 (5.3%) had schisis detachment, 66 (23.5%) had macular retinoschisis alone, and 5 (1.8%) had combined macular and peripheral retinoschisis. Of the eyes without macular retinoschisis, 7.0% had schisis detachment. Of the remainder, 4 (2.1%) had inner wall breaks, and 24 (12.3%) had outer wall breaks. In eyes with peripheral retinoschisis, splitting occurred in the outer plexiform layer in 58.9%, the retinal nerve fiber layer in 8.9%, a combination of layers in 26.8%, and indeterminate in 5.4%. Location of peripheral involvement was inferotemporal in 58.5%, superotemporal in 14.1%, temporal in 13.7%, and inferior in 12.2%. CONCLUSION: SD-OCT helped to identify the presence of schisis detachment and breaks, confirmed diagnosis in challenging cases, and demonstrated the layer of splitting within the neurosensory retina. This series represents the largest such study to date.

Bilateral bullous central serous chorioretinopathy treated with PDT and eplerenone.

Purpose: To report a case evaluating PDT and eplerenone therapy in a patient with bilateral bullous central serous chorioretinopathy. Observations: A 30-year-old male was referred for worsening bilateral bullous central serous chorioretinopathy (bCSCR) despite oral eplerenone therapy. Photodynamic therapy (PDT) was performed in the right eye with significant improvement of bullous retinal detachment, near-complete resolution of subfoveal subretinal fluid, and improvement of vision from 20/200 to 20/25. The left eye had persistent subretinal fluid despite continued eplerenone therapy. Neither eye worsened when eplerenone was withdrawn. Total follow up was 3.5 years. Conclusions and Importance: This case demonstrates a significant and durable effect of PDT in bullous CSCR and suggests a lack of response to eplerenone.

Phenotypic variant of CLN3 mutation.

Purpose: To report a case of bilateral chorioretinal scarring due to CLN3 heterozygous deletion in an asymptomatic patient. Observations: A 63 year-old patient with a history of well-controlled diabetes presented as a referral for diabetic retinopathy. He was asymptomatic with 20/20 visual acuity in both eyes. Exam revealed bilateral multifocal chorioretinal scarring left worse than right, sparing the fovea. He was unable to provide a family history due to adoption, and his remaining medical history and review of systems were noncontributory. Inflammatory and infectious workup was negative; however, genetic testing revealed heterozygous deletion of CLN3 exons 8 and 9. His disease has been nonprogressive at all follow-up appointments. Conclusions and importance: Mutations of CLN3 can present with retina-specific findings including bull's-eye maculopathy and electroretinogram (ERG) deficits; to our knowledge this patient's presentation is unique among those with CLN3 mutations.

TREATMENT OF BILATERAL DIFFUSE UVEAL MELANOCYTIC PROLIFERATION WITH INTRAVITREAL STEROID IMPLANTS.

BACKGROUND/PURPOSE: To report a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) treated with intravitreal steroid implants. METHOD: Bilateral diffuse uveal melanocytic proliferation was diagnosed and treated with intravitreal steroid implants (both dexamethasone 0.7 mg [intravitreal dexamethasone implants] and fluocinolone acetonide 0.18 mg [intravitreal fluocinolone acetonide implants]) and monitored every 2 weeks to 4 weeks with optical coherence tomography. RESULTS: Intravitreal dexamethasone implants improved visual acuity and central retinal thickness for 10 weeks, was best from 4 to 6 weeks, and recurred by 14 weeks after treatment. Intravitreal fluocinolone acetonide implants improved visual acuity and central retinal thickness for 20 weeks after treatment without edema recurrence. No retinal detachments were observed over 1 year of treatment. CONCLUSION: Intravitreal steroid implants resulted in visual acuity improvement and central retinal thickness reduction for up to 20 weeks and may protect against retinal detachments in patients with bilateral diffuse uveal melanocytic proliferation.

Lymphoma masquerading as occlusive retinal vasculitis: A case study.

PURPOSE: To describe a case of retinal lymphoma presenting as an occlusive retinal vasculitis without vitritis that was exquisitely responsive to intravitreal dexamethasone implant (IVDI). OBSERVATION: A 66-year old male presented with decreased vision in the right eye and was diagnosed with occlusive retinal vasculitis and prominent cystoid macular edema though he lacked vitritis. A complete systemic workup for infectious, inflammatory, and infiltrative etiologies was unremarkable. Intravenous methylprednisolone and cyclophosphamide had no clinical effect. Due to persistent perivascular exudates and refractory macular edema, IVDI was administered with marked improvement in vision and clinical findings. Subsequent retinal vasculitis in the left eye responded to IVDI as well. The patient remained disease free for months while on weekly adalimumab. He then presented with acute vision loss in the left eye due to a lymphomatous subretinal infiltration and a new lesion in the corpus callosum. He has remained disease free for more than two years after intravitreal methotrexate injections and rituximab with an autologous stem cell transplant. CONCLUSION AND IMPORTANCE: Lymphoma may present as an occlusive retinal vasculitis without vitritis and can be masked due to its response to IVDI.

Acute Angle Closure Precipitated by Hemorrhage and Necrosis of a Large Uveal Melanoma in the Setting of Systemic Immunomodulatory Therapy.

Management of nonmetastatic uveal melanoma has been well studied and a large body of work has been published by the Collaborative Ocular Melanoma Study (amongst many others). Management of uveal melanoma that is found to be metastatic upon initial diagnosis, however, is less well defined. We report an interesting case of acute angle closure caused by necrosis and hemorrhage into a large uveal melanoma occurring shortly after initiation of immunomodulatory therapy with ipilimumab and nivolumab for metastatic disease. The use of these immunomodulatory agents in the setting of metastatic uveal melanoma is not well studied, and our case illustrates the importance of interdisciplinary communication in order to best decide the timing of surgical and systemic medical management to optimize outcomes and minimize morbidity.

Bull's eye maculopathy in an HIV-positive patient receiving ritonavir.

Retinal toxicity involving the macula as a complication of the antiretroviral protease inhibitor ritonavir has been described in a few cases. We report retinal pigment epitheliopathy involving the macula with a bull's eye pattern in a 36-year-old man with well-controlled HIV receiving ritonavir with gradually progressive bilateral vision loss.

Intravitreal Aflibercept for Neovascular AMD: Short-Term Clinical Effects of Intravitreal Aflibercept Injection as a Predictor of Long-Term Results.

BACKGROUND AND OBJECTIVE: To study the relationship between early response to intravitreal aflibercept injection (IAI) for neovascular age-related macular degeneration (nAMD) and long-term visual outcomes PATIENTS AND METHODS: Seventeen patients with nAMD participated in this prospective clinical trial. All patients received three initial monthly IAIs, followed by IAIs at 8-week intervals. Study visits were scheduled at 1 week, followed by every 2 weeks for the first 3 months and then every 4 weeks until the conclusion of the study at 48 weeks. RESULTS: Eight eyes (47%) were dry on spectral-domain optical coherence tomography by week 2 (early responders), and the remaining nine eyes took an average of 7.5 weeks for fluid resolution (late responders). The mean change in best-corrected visual acuity (BCVA) at the final visit was +11.9 letters from baseline (P = .002). Average BCVA gain in early responders was +11.6 letters compared to +12.2 letters in late responders (P = .7). CONCLUSIONS: Although there was not a statistically significant correlation between early response to IAI and better long-term outcomes, both early and late responders maintained excellent visual outcomes at 48 weeks.

Bevacizumab Versus Ranibizumab in the Treatment of Macular Edema Due to Retinal Vein Occlusion: 6-Month Results of the CRAVE Study.

BACKGROUND AND OBJECTIVE: To compare efficacy of monthly treatment with bevacizumab or ranibizumab for macular edema due to retinal vein occlusion. PATIENTS AND METHODS: Randomized, multicenter, comparative trial (ClinicalTrials.gov identifier: NCT01428388). Participants were randomized 1:1 to receive monthly treatment with bevacizumab or ranibizumab. The primary outcome was change in central foveal thickness at 6 months compared to baseline. RESULTS: The trial randomized 98 patients to treatment with bevacizumab or ranibizumab. At 6 months, there were no differences in change in central foveal thickness between groups (bevacizumab: mean reduction of 212.6 µm, 95% confidence interval [CI], -288.3 to -137.0; ranibizumab: mean reduction of 243.8 µm, 95% CI, -309.6 to -178.0; P=.72, analysis of variance [ANOVA]). Both groups showed similar functional outcomes (bevacizumab: 0.33 logMAR gain, 95% CI, -0.47 to -0.18; ranibizumab: 0.34 logMAR gain, 95% CI, -0.45 to -0.23; P=.38, ANOVA). CONCLUSION: In the treatment of retinal vein occlusion, bevacizumab and ranibizumab have similar effects on reducing macular thickness and improving visual acuity.

Labor-induced hemorrhage of a retinal cavernous hemangioma.

The authors present a case of a previously undiagnosed retinal cavernous hemangioma that hemorrhaged during labor. There are previous reports of labor-induced intracranial hemorrhage from central nervous system vascular malformations, but none have demonstrated intraocular hemorrhage during labor. The case emphasizes a need to screen patients with retinal cavernous hemangioma and to warn them of possible vision loss during Valsalva maneuvers such as labor.

Retinal pigment epithelial tears in ranibizumab-treated eyes.

PURPOSE: To report the incidence of retinal pigment epithelial (RPE) tears in patients treated with ranibizumab therapy for choroidal neovascularization due to age-related macular degeneration. DESIGN: : Interventional case series. METHODS: One hundred sixty-four eyes from a large clinical practice were retrospectively reviewed for number of injections and the presence or absence of a fibrovascular retinal pigment epithelial detachment. Main outcome measures were occurrence of RPE tears, and timing of tears following the last injection. RESULTS: Patients were observed for an average of 11 months. A single patient (0.61%) experienced an RPE tear and this occurred after the first injection. In eyes with a fibrovascular retinal pigment epithelial detachment the incidence was 5%. Lesions containing a fibrovascular retinal pigment epithelial detachment tended to be larger (4.5 versus 3.8 Macular Photocoagulation Study Disc Areas), but this was not statistically significant. (P = 0.63). However, these lesions required more injections on average (P = 0.05). CONCLUSION: The incidence of RPE tears associated with ranibizumab therapy is low and may result from a predisposition rather than an effect of treatment. Even so, patients undergoing ranibizumab therapy should be counseled regarding this possible complication.

Intravitreal injection of bevacizumab combined with verteporfin photodynamic therapy for choroidal neovascularization in age-related macular degeneration.

PURPOSE: To report the outcome for eyes treated with intravitreal injection of bevacizumab combined with verteporfin photodynamic therapy (PDT) for choroidal neovascularization (CNV) in age-related macular degeneration (AMD). STUDY DESIGN AND PARTICIPANTS: Interventional, consecutive, retrospective case series including 40 eyes of 40 patients with newly diagnosed juxtafoveal or subfoveal CNV secondary to AMD. METHODS: The charts of patients treated with a 1.25-mg intravitreal injection of bevacizumab followed by PDT within a 2-week period were reviewed. Main outcome measures were visual acuity stabilization (defined as no change or a gain in visual acuity) and need for retreatment. RESULTS: Thirty-three (83%) of 40 eyes had stabilization of visual acuity. Mean improvement in visual acuity was 1.73 lines. Twenty-six eyes (65%) required only a single intravitreal injection of bevacizumab combined with PDT. Of the 23 eyes with 12 months of follow-up, 17 (74%) had stabilization of visual acuity, while 9 (40%) had improvement in visual acuity (mean, 1.22 Snellen lines). Eleven eyes (48%) required only a single combined treatment for CNV resolution at the 12-month follow-up. Fifteen (88%) of 17 eyes with only 6 months of follow-up required only a single combined treatment. There were no complications such as endophthalmitis, uveitis, or ocular hypertension. CONCLUSION: These findings suggest that eyes treated with both intravitreal injection of bevacizumab and PDT require none to a minimal number of re-treatments to have stabilization of vision, even at 12 months of follow-up. Further investigation with large controlled trials is warranted to outline the appropriate treatment paradigm for combination therapy.

Intravitreal bevacizumab for choroidal neovascularization in ocular histoplasmosis.

PURPOSE: To define the role of intravitreal bevacizumab in individuals with choroidal neovascularization (CNV) resulting from Ocular Histoplasmosis syndrome (OHS). DESIGN: Retrospective chart review of a surgical therapy. METHODS: We reviewed the course of 28 eyes of 28 patients who underwent intravitreal injection of bevacizumab for treatment of CNV secondary to OHS. Outcome was measured by pretreatment and posttreatment visual acuity (VA). RESULTS: The average pretreatment logarithm of the minimum angle of resolution (logMAR) VA was 0.65 (Snellen equivalent of 20/88). Mean follow-up was 22.43 weeks with an average of 1.8 intravitreal injections. Average final logMAR VA was 0.43 (Snellen equivalent of 20/54). Twenty eyes (71%) experienced an increase in central VA, whereas four eyes (14%) were unchanged and four eyes (14%) experienced a decrease in vision. CONCLUSIONS: Intravitreal bevacizumab may improve or stabilize VA in a significant majority of patients with neovascular complications of OHS (24 eyes [85.7%] in our study population).

Incentives for biodefense countermeasure development.

Therapeutics and vaccines are available for only a fraction of biological threats, leaving populations vulnerable to attacks involving biological weapons. Existing U.S. policies to accelerate commercial development of biodefense products have thus far induced insufficient investment by the biopharmaceutical industry. In this article, we examine the technical, regulatory, and market risks associated with countermeasure development and review existing and proposed federal incentives to increase industrial investment. We conclude with several recommendations. To increase industry's engagement in biodefense countermeasure development, Congress should expand BioShield funding, giving HHS the flexibility to fund a portfolio of biodefense countermeasures whose revenues are comparable to those of commercial drugs. Congress should establish tradable priority review vouchers for developers of new countermeasures. A National Academy of Sciences or National Biodefense Science Board should formally evaluate incentive programs and a government-managed "Virtual Pharma," in which HHS contracts separate stages of research, development, and production to individual firms.