The Impact of COVID-19 on US and International Retina Specialists, Their Practices, and Their Patients.

Purpose: This work analyzes data from a series of surveys developed by the American Society of Retina Specialists (ASRS) that assesses the impact of COVID-19 on physicians, their practices, and their patients. Methods: Five surveys were sent by the ASRS between March and July 2020 to more than 2600 US and international retina specialists. Data and trends from these surveys were analyzed. Results: Most responding retina specialists (87%-95% in the United States and internationally) reported having no known COVID-related symptoms despite reported limitations in personal protective equipment. Clinic volumes globally were drastically reduced in March 2020 with only partial recovery through July 2020, which was slower internationally than in the United States. Practices were compelled to reduce staff and physician employment levels. Most respondents estimated some degree of delay in patient treatment with corresponding declines in vision and/or anatomy that were attributed most frequently to patients' fears of the pandemic and least frequently to office unavailability. Conclusions: The reported impact of COVID-19 on retina specialists, their practices, and their patients has been substantial. Although retina specialists were quickly resilient in optimizing delivery of patient care in a manner safe for patients and providers, the reduction in clinic volume has been devastating in the United States and internationally, with negative impacts on patient outcomes, reductions in practices' volume and employment, and risk to practices' financial health. Future studies will be required to quantify losses associated with these unprecedented and ongoing circumstances caused by the pandemic.

Torpedo-like lesions in the ocular fundi of Gardner syndrome: hiding in plain view.

Background: The coexistence of fundus torpedoes and Gardner syndrome was initially reported in 1989 and 1992 by Gass and Roseman. Gardner syndrome is a dominantly inherited disease characterized by a multitude of potentially lethal gastrointestinal polyps. Over the ensuing quarter century, several publications demonstrated uncommon, but easily recognized, fundus lesions called Torpedo Maculopathy in apparently normal individuals. These fundus abnormalities were thought to be single and isolated without systemic associations. During the same period of time, a variety of nonspecific fundus abnormalities were described in Gardner syndrome, which, in retrospect, included highly specific lesions that closely resembled macular torpedoes and sometimes were indistinguishable from them.Patient and methods: We now report a confirmed case of Gardner syndrome with numerous fundus torpedoes, and carefully analyze the voluminous literature of both Gardner syndrome and Torpedo Maculopathy.Results: We demonstrate shared features of the fundus lesions in both diseases, and hypothesize that they may have genetic as well as ophthalmoscopic similarities in common.Conclusions: We therefore recommend that individuals with classic isolated torpedoes undergo evaluations for mutations in the Gardner gene (Adenomatous polyposis coli) and for the presence of gastrointestinal polyps and other systemic features of Gardner syndrome. We also suggest that apparently normal individuals, who are genetically related to patients with known classic torpedoes, undergo inspection of their fundi for the possible presence of characteristic lesions.

Ocular Histopathology and Immunohistochemical Analysis in the Oldest Known Individual with Autosomal Dominant Vitreoretinochoroidopathy.

PURPOSE: To assess the immunohistochemical and histopathological changes in a subject with Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC). DESIGN: Case study. PARTICIPANT: Ninety two year-old Caucasian male with ADVIRC. METHODS: The subject was documented clinically for 54 Years. The retina/choroid complex of the right eye was evaluated with cryosections stained with hematoxylin and eosin or periodic acid schiff reagent. Cryosections were also evaluated with immunofluorescence or alkaline phosphatase immunohistochemistry (IHC) using primary antibodies against bestrophin1, GFAP, PEDF, RPE65, TGFß, VEGF, and vimentin. The left retina and choroid were evaluated as flat mounts using immunofluorescence. UEA lectin was used to stain viable vasculature. MAIN OUTCOME MEASURES: The immunohistochemical and histopathological changes in retina and choroid from a subject with ADVIRC. RESULTS: The subject had a heterozygous c.248G>A variant in exon 4 of the BEST1 gene. There was widespread chorioretinal degeneration and atrophy except for an island of spared RPE monolayer in the perimacula/macula OU. In this region, some photoreceptors were present, choriocapillaris was spared, and retinal pigment epithelial cells were in their normal disposition. There was a Muller cell periretinal membrane throughout much of the fundus. Bestrophin-1 was not detected or only minimally present by IHC in the ADVIRC RPE, even in the spared RPE area. Beyond the island of retained RPE monolayer on Bruch's membrane (BrMb), there was migration of RPE into the neuro-retina, often ensheathing blood vessels and producing excessive matrix within their perivascular aggregations. CONCLUSIONS: The primary defect in ADVIRC is in RPE, the only cells in the eye that express the BEST1 gene. The dysfunctional RPE cells may go through epithelial/mesenchymal transition as they migrate from BrMb to form papillary aggregations in the neuro-retina, often ensheathing blood vessels. This may be the reason for retinal blood vessel nonperfusion. Migration of RPE from BrMb was also associated with attenuation of the choriocapillaris.

Long-Term Macular Changes in the First Proband of Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC) Due to a Newly Identified Mutation in BEST1.

BACKGROUND: Mutations in BEST1 account for autosomal dominant vitreoretinochoroidopathy (ADVIRC), a rare inherited retinal dystrophy with presenile cataracts and incomplete anterior segment development. The long-term clinical findings and visual prognosis of these patients continues to evolve over time. MATERIALS AND METHODS: The retina was assessed by fundus photography, fluorescein angiography, and spectral domain optical coherence tomography. Sanger dideoxy chain-termination sequencing identified mutations in BEST1. Bioinformatic tools were used to predict changes in splicing. An in vitro splicing assay was applied to evaluate for altered pre-mRNA splicing. RESULTS: Long-term follow up of the first ever reported ADVIRC proband revealed progressive foveal atrophy in both eyes 3 decades after his initial presentation. Progressive retinal ischemia, bilateral iris atrophy, and pseudophakodnesis were observed on follow up. The patient was heterozygous for a c.248G > A missense mutation in exon 4 of BEST1, affecting a highly conserved transmembrane domain. Although computational prediction models suggest a change in the binding probability of splicing-associated SR proteins, in vitro splicing assays failed to demonstrate an effect of the c.248G > A mutation on splicing of BEST1 exon 3 or exon 4. CONCLUSIONS: Progressive posterior chorioretinal changes occurred over time in the initial ADVIRC proband, leading to visual loss. The causative mutation in this patient falls in the transmembrane domain of the BEST1 protein, with unclear functional consequences. Although previous studies showed alteration in pre-mRNA splicing, in vitro splicing assays failed to demonstrate this in our patient.

Improving Outcomes for Patients With Diabetic Macular Edema.

Diabetic macular edema (DME) is one of the most common causes of vision loss in patients who have diabetes, and all of these patients are at risk for developing DME. The onset is often painless, difficult to detect, and can occur at any stage of diabetes. Ideally, DME is preventable, but treatment must be considered when preventative methods fail. Although physicians have several different treatment options for patients with DME, some patients who receive treatment can respond poorly and may even lose vision. Until recently, laser photocoagulation was regarded as the standard of care for DME; however, pharmaceutical treatments are rapidly replacing this standard as the desire to maximize systemic treatment of DME increases. A panel of experts gathered during the 2015 annual meeting of the Association for Research in Vision and Ophthalmology for a roundtable discussion designed to focus on improving outcomes for patients with DME using pharmaceutical treatment, including the use of anti-VEGFs and corticosteroids, based on the most current research and clinical data.

Stellate nonhereditary idiopathic foveomacular retinoschisis.

PURPOSE: To describe a new classification of stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR). DESIGN: Retrospective case series and literature review. PARTICIPANTS: A total of 17 patients from 5 institutions. METHODS: Detailed case history, multimodal imaging, and genetic testing were reviewed for patients with macular schisis without a known predisposing condition. Patients with a stellate appearance centered on the fovea with correlating confirmed expansion of the outer plexiform layer (OPL) by optical coherence tomography (OCT) were included. Exclusion criteria included a family history of macular retinoschisis, a known genetic abnormality associated with retinoschisis, myopic traction maculopathy, epiretinal membrane, vitreoretinal traction, optic or scleral pit, or advanced glaucomatous optic nerve changes. MAIN OUTCOME MEASURES: Clinical features, anatomic characteristics, and visual acuity. RESULTS: A total of 22 eyes from 16 female patients and 1 male patient with foveomacular schisis were reviewed from 5 institutions. Initial visual acuity was ≥ 20/50 in all eyes (mean, 20/27), but visual acuity in a single eye decreased from 20/20 to 20/200 after the development of subfoveal fluid. The refractive status was myopic in 16 eyes, plano in 3 eyes, and hyperopic in 2 eyes. Three eyes had a preexisting vitreous separation, and 19 eyes had an attached posterior hyaloid. Follow-up ranged from 6 months to >5 years. CONCLUSIONS: In this largest known series of patients with SNIFR, all patients demonstrated splitting of the OPL in the macula with relatively preserved visual acuity (≥ 20/40) except in a single patient in whom subretinal fluid developed under the fovea.

Spontaneous anatomical and visual improvement in myopic macular retinoschisis.

Myopic macular retinoschisis is a source of visual impairment in patients with high myopia. Many patients present with progressive visual loss or increasing distortion. Some eyes progress to macular hole or foveal retinal detachment, causing further vision loss. The mechanisms for development of myopic macular retinoschisis have been postulated to be from tractional forces exerted on the inner retina, either anteriorly from a shortened internal limiting membrane and the retinal vessels or posteriorly from staphylomatous changes. Surgical intervention is often indicated for patients with declining visual function. The authors report a case of myopic macular retinoschisis that spontaneously improved without surgical intervention.

Chronic central serous chorioretinopathy responsive to rifampin.

PURPOSE: The purpose of this was to describe the clinical improvement of chronic central serous chorioretinopathy in a patient treated with rifampin for tuberculosis. METHODS: A 54-year-old Hispanic man with a distant history of pulmonary tuberculosis presented with reduced vision in the right greater than left eye for over 1 year. He had diffuse chorioretinopathy in both eyes and a serous retinal detachment in his right eye. The findings were most consistent with chronic central serous chorioretinopathy, although tuberculosis -related choroiditis could not be excluded. Treatment with multidrug antituberculosis medications, including rifampin, resulted in the reduction in leakage and resolution of subretinal fluid. Fluid recurred on cessation of all medications and resolved again with retreatment. Monotherapy with rifampin maintained the absence of fluid. DISCUSSION: This case represents the first report of chronic central serous chorioretinopathy responding to systemic therapy with rifampin. We hypothesize that the clinical response observed is secondary to induction of cytochrome P450 with increased hepatic metabolism of endogenous corticosteroids and a reduction in systemic cortisol levels.

Orbital migration of gas in a case of colobomatous microphthalmos.

PURPOSE: The purpose of the study was to report a unique case that suggests a communication between a colobomatous eye and the orbit. METHODS: Case report. PATIENTS: Eleven-year-old girl. RESULTS: Gas moved from the vitreous cavity into the orbit during vitrectomy in a colobomatous microphthalmic eye. CONCLUSION: As this case suggests, there may be an occult connection through the coloboma and the surrounding extraocular tissue, possibly providing an additional etiology of subretinal fluid that can be associated with these congenital optic nerve disorders.

A placebo-controlled trial of microplasmin intravitreous injection to facilitate posterior vitreous detachment before vitrectomy.

PURPOSE: To evaluate the safety and efficacy of a preoperative intravitreous injection of microplasmin in patients scheduled for vitreous surgery. DESIGN: Phase 2, multicenter, placebo-controlled, double-masked, parallel-group, dose-ranging clinical trial. PARTICIPANTS: One hundred twenty-five patients scheduled for pars plana vitrectomy (PPV), primarily for treatment of either vitreomacular traction or macular hole. INTERVENTION: A single intravitreous injection of either microplasmin at 1 of 3 doses (25 microg, 75 microg, or 125 microg in 100 microl) or placebo injection administered 7 days before PPV. MAIN OUTCOME MEASURES: Presence or absence of posterior vitreous detachment (PVD) at the time of PPV, progression of PVD, and resolution of vitreomacular interface abnormality precluding the need for PPV. RESULTS: Rates of total PVD at the time of surgery were 10%, 14%, 18%, and 31% in the placebo group (n = 30), 25-microg (n = 29), 75-microg (n = 33), and 125-microg microplasmin groups (n = 32), respectively. The secondary end point resolution of vitreomacular interface abnormality precluding the need for vitrectomy at the 35-day time point was observed at rates of 3%, 10%, 15%, and 31% in the placebo, and the 25-microg, the 75-microg, and the 125-microg microplasmin groups, respectively. At the 180-day time point, the equivalent rates were 3%, 7%, 15%, and 28%, respectively. CONCLUSIONS: Microplasmin injection at a dose of 125 microg led to a greater likelihood of induction and progression of PVD than placebo injection. Patients receiving microplasmin were significantly more likely not to require vitrectomy surgery. More definitive evaluation in phase 3 clinical trials therefore is warranted. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Preferential Hyperacuity Perimeter (PreView PHP) for detecting choroidal neovascularization study.

PURPOSE: To assess the ability of the Preferential Hyperacuity Perimeter (PreView PHP; Carl Zeiss Meditec, Dublin, CA) to detect recent-onset choroidal neovascularization (CNV) resulting from age-related macular degeneration (AMD) and to differentiate it from an intermediate stage of AMD. DESIGN: Prospective, comparative, concurrent, nonrandomized, multicenter study. PARTICIPANTS: Eligible participants' study eyes had a corrected visual acuity of 20/160 or better and either untreated CNV from AMD diagnosed within the last 60 days or an intermediate stage of AMD. METHODS: After obtaining consent, visual acuity with habitual correction, masked PHP testing, stereoscopic color fundus photography, and fluorescein angiography were performed. Photographs and angiograms were evaluated by graders masked to diagnosis and PHP results. The reading center's diagnosis determined if the patient was categorized as having intermediate AMD or neovascular AMD. MAIN OUTCOME MEASURES: A successful study outcome was defined a priori as a sensitivity of at least 80% and a specificity of at least 80%. RESULTS: Of 185 patients who gave consent to be enrolled, 11 (6%) had PHP results judged to be unreliable. An additional 52 were not included because they did not meet all eligibility criteria. Of the remaining 122 patients, 57 had an intermediate stage of AMD and 65 had neovascular AMD. The sensitivity to detect newly diagnosed CNV using PHP testing was 82% (95% confidence interval [CI], 70%-90%). The specificity to differentiate newly diagnosed CNV from the intermediate stage of AMD using PHP testing was 88% (95% CI, 76%-95%). CONCLUSIONS: Preferential Hyperacuity Perimeter testing can detect recent-onset CNV resulting from AMD and can differentiate it from an intermediate stage of AMD with high sensitivity and specificity. These data suggest that monitoring with PHP should detect most cases of CNV of recent onset with few false-positive results at a stage when treatment usually would be beneficial. Thus, this monitoring should be considered in the management of the intermediate stage of AMD.

Subretinal recombinant tissue plasminogen activator injection and pneumatic displacement of thick submacular hemorrhage in Age-Related macular degeneration.

OBJECTIVE: To evaluate the anatomic and visual outcomes after a surgical procedure for displacement of thick submacular hemorrhage in patients with age-related macular degeneration. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Twenty-nine consecutive eyes of 28 patients with thick submacular hemorrhage secondary to age-related macular degeneration. INTERVENTION: The procedure consisted of a pars plana vitrectomy with subretinal recombinant tissue plasminogen activator injection (125 micrograms/ml) through a translocation microcannula, followed by fluid-air exchange and postoperative prone positioning [correction]. MAIN OUTCOME MEASURES: Intraoperative and postoperative surgical complications, preoperative and postoperative best-corrected visual acuities, postoperative fluorescein angiography results, and additional postoperative treatments. RESULTS: Total subfoveal blood displacement was achieved in 25 eyes, with subtotal displacement in the others. Based on fluorescein angiography results, 8 eyes were eligible for additional postoperative treatments. At 3 months, 17 eyes had gained more than 2 lines of visual acuity, whereas 3 had lost more than 2 lines. The difference between preoperative and 3-month postoperative visual acuity was statistically significant (P = 0.0167). Complications consisted of 2 cases of vitreous hemorrhage that cleared within 4 weeks. CONCLUSIONS: This surgical technique seems useful in displacing thick submacular hemorrhage secondary to age-related macular degeneration, allowing postoperative fluorescein angiography testing and, potentially, subsequent treatments. No significant complication from the procedure was identified. However, further controlled studies will be required to assess its efficacy in the management of this difficult clinical problem.

The artificial silicon retina microchip for the treatment of vision loss from retinitis pigmentosa.

OBJECTIVE: To determine the safety and efficacy of the artificial silicon retina (ASR) microchip implanted in the subretinal space to treat vision loss from retinitis pigmentosa. METHODS: The ASR microchip is a 2-mm-diameter silicon-based device that contains approximately 5000 microelectrode-tipped microphotodiodes and is powered by incident light. The right eyes of 6 patients with retinitis pigmentosa were implanted with the ASR microchip while the left eyes served as controls. Safety and visual function information was collected. RESULTS: During follow-up that ranged from 6 to 18 months, all ASRs functioned electrically. No patient showed signs of implant rejection, infection, inflammation, erosion, neovascularization, retinal detachment, or migration. Visual function improvements occurred in all patients and included unexpected improvements in retinal areas distant from the implant. MAIN OUTCOME MEASURES: Subjective improvements included improved perception of brightness, contrast, color, movement, shape, resolution, and visual field size. CONCLUSIONS: No significant safety-related adverse effects were observed. The observation of retinal visual improvement in areas far from the implant site suggests a possible generalized neurotrophic-type rescue effect on the damaged retina caused by the presence of the ASR. A larger clinical trial is indicated to further evaluate the safety and efficacy of a subretinally implanted ASR.

Preservation of anterior capsule during vitrectomy and lensectomy for retinal detachment with proliferative vitreoretinopathy.

PURPOSE: To report a series of 15 eyes with rhegmatogenous retinal detachment and proliferative vitreoretinopathy (PVR) or at high risk for advanced PVR, which underwent pars plana vitrectomy (PPV) and lensectomy (PPL) with preservation of the anterior capsule. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Fifteen consecutive patients with retinal detachment and varying degrees of PVR in one eye. METHODS: All eyes had undergone PPV and PPL with preservation and polishing of the anterior capsule and had at least 6 months of follow-up. Of the 15 eyes, grade C PVR was present preoperatively in 11 and was anterior in 5. Seven of 15 eyes had gas and 8 of 15 had silicone oil tamponade. Eight of 15 eyes had subsequent posterior chamber intraocular lens (PCIOL) placement; 5 eyes had simultaneous silicone oil removal. One eye had a PCIOL placed at the time of the PPL. MAIN OUTCOME MEASURES: Visual acuity, retinal reattachment, complications of gas or silicone oil tamponade, and anterior capsular clarity. RESULTS: Fourteen eyes had complete retinal reattachment at the final visit (1 of 15 had macular redetachment only). Final visual acuity was better or equal to preoperative acuity in all eyes, improving by 4 +/- 4 lines overall. No eyes had corneal decompensation, pupillary block, or other vision-threatening anterior segment complication. The anterior capsule remained centrally clear in the 13 eyes that did not have a primary central capsulotomy. One eye with minimal preoperative PVR developed hypotony. CONCLUSIONS: Vitreoretinal surgeons can preserve the anterior capsule in eyes with retinal detachment and PVR to help prevent intraoperative and postoperative complications of gas or silicone oil, simplify future PCIOL placement, and maintain a normal iris appearance.