SUPRACHOROIDAL SPACE INJECTION TECHNIQUE: Expert Panel Guidance.

PURPOSE: To develop professional guidelines for best practices for suprachoroidal space (SCS) injection, an innovative technique for retinal therapeutic delivery, based on current published evidence and clinical experience. METHODS: A panel of expert ophthalmologists reviewed current published evidence and clinical experience during a live working group meeting to define points of consensus and key clinical considerations to inform the development of guidelines for in-office SCS injection. RESULTS: Core consensus guidelines for in-office SCS injection were reached and reported by the expert panel. Current clinical evidence and physician experience supported SCS injection as a safe and effective method for delivering retinal and choroidal therapeutics. The panel established consensus on the rationale for SCS injection, including potential benefits relative to other intraocular delivery methods and current best practices in patient preparation, pre- and peri-injection management, SCS-specific injection techniques, and postinjection management and follow-up. CONCLUSION: These expert panel guidelines may support and promote standardization of SCS injection technique, with the goal of optimizing patient safety and outcomes. Some aspects of the procedure may reasonably be modified based on the clinical setting and physician judgment, as well as additional study.

Bullous Variant of Central Serous Chorioretinopathy in Goodpasture's Disease - A Case Report and Review of Literature.

PURPOSE: To describe a case of bullous variant of central serous chorioretinopathy (CSR) in Goodpasture's disease (GD) compared to an identical twin without GD, and summarize the literature on ocular manifestations of GD. METHODS: Interventional/observational case report and literature review. RESULTS: A 46-year-old white female with a history of GD presented with decreased vision. She demonstrated bilateral multifocal pigment epithelial detachments and a large inferior exudative retinal detachment in the left eye consistent with bilateral CSR with bullous variant CSR (bvCSR) in the left eye. Despite treatment, her disease remained refractory, with final VA of 20/200 in the left eye. The patient's identical twin sister did not have GD and demonstrated milder CSR on presentation with a more typical, self-limited disease course. Her final VA was 20/20 bilaterally. CONCLUSION: GD is associated with severe manifestations of CSR (exudative RD). Additional studies focusing on the association between GD and CSR severity may be of interest.

Bilateral uveitis, retinal periphlebitis, and optic neuritis associated with non-pineal central nervous system germinoma.

PURPOSE: To report a case of bilateral uveitis, retinal periphlebitis, and optic neuritis associated with a non-pineal central nervous system (CNS) germinoma. METHODS: Case report. RESULTS: A 32-year-old male presented with episodes of acute painless visual disturbance in each eye, and was found to have decreased visual acuity, abnormal color vision, an afferent pupillary defect in the left eye, bilateral optic disc edema, perivenous sheathing, and candle-wax dripping exudates. Optical coherence tomography revealed bilateral intraretinal fluid and posterior vitreous hyperreflective opacities. Fluorescein angiography revealed bilateral optic disc leakage without active small vessel leakage. Magnetic resonance imaging of the brain and orbits revealed enhancing periventricular lesions and enhancement of the left optic nerve and bilateral perioptic nerve sheaths, posterior globes, and optic nerve heads. Brain biopsy was consistent with a CNS germinoma. His ocular signs and symptoms improved with chemotherapy for the germinoma. CONCLUSION: CNS germinomas, including those located outside the pineal region, can be associated with optic neuritis, uveitis, and periphlebitis including characteristic candle-wax dripping exudates. Ocular signs and symptoms typically improve with treatment of the underlying germinoma.

OUTER RETINOPATHY AND MICROANGIOPATHY IN ACUTE MYELOGENOUS LEUKEMIA.

PURPOSE: To describe a patient with acute myelogenous leukemia who presented with a recurrent, bilateral, outer retinopathy, before and after consolidative peripheral blood stem cell transplantation complicated by chronic graft-versus-host disease. METHODS: This is a retrospective review of records from a 23-year-old woman with acute myelogenous leukemia who underwent comprehensive ophthalmic evaluations for over a year including chromatic perimetry and multifocal electroretinograms, imaging with spectral domain optical coherence tomography, near-infrared and short-wavelength fundus reflectance and autofluorescence, fluorescein and optical coherence tomography angiography. RESULTS: The patient presented with recurrent, unilateral paracentral scotomas. There was localized loss of inner segment ellipsoid (EZ) and photoreceptor outer segment signals (IZ) in the pericentral retina of both eyes co-localizing with hyperreflective lesions on near-infrared reflectance. She subsequently lost vision (visual acuity = 20/200) in the right eye a year after consolidative peripheral blood stem cell transplantation complicated by steroid-resistant-chronic graft-versus-host disease. There was loss of the EZ and IZ signals corresponding to a dense central cone scotoma and multifocal electroretinograms depression. Near-infrared autofluorescence, fluorescein and optical coherence tomography angiography were within normal limits. Visual acuity (20/20) and retinal sensitivities improved with restoration of the EZ/IZ signals after oral prednisone and intravenous rituximab, but left a residual photoreceptor loss and paracentral scotoma. CONCLUSION: We propose that an immune-mediated microangiopathy may explain the protracted, recurrent course of primary photoreceptor abnormalities in our patient, which was further complicated by manifestations of chronic graft-versus-host disease following consolidative peripheral blood stem cell transplantation. Outer retinal findings previously documented in leukemia may be explained by a similar mechanism.

Bilateral retinal hemorrhages after sequential endovascular treatment of bilateral unruptured cerebral aneurysms.

PURPOSE: To report a case of bilateral retinal hemorrhages in a patient undergoing two separate endovascular interventions for bilateral cerebral aneurysms. METHODS: A comprehensive ophthalmic examination was performed after the patient underwent each of two separate endovascular interventions for bilateral cerebral aneurysms. Multimodal imaging including widefield pseudocolor fundus photography, optical coherence tomography, and widefield fluorescein angiography (FA) was obtained. A systemic workup including genetic testing and hypercoagulability studies was performed. RESULTS: Dilated fundus examination revealed new visually significant ipsilateral retinal hemorrhages after each endovascular procedure. FA showed evidence of a peripheral retinal microangiopathy present in both eyes before the patient underwent her second endovascular procedure. Systemic workup revealed persistently elevated serum anticardiolipin IgM antibody levels at >99th percentile. CONCLUSION: Retinal complications after endovascular intracranial interventions are uncommon. This patient who developed bilateral retinal complications was found to have persistently elevated anticardiolipin antibody levels, a risk factor for thrombosis. Patients who develop retinal complications after endovascular intracranial intervention may benefit from systemic workup for hypercoagulable conditions.

Vitreoretinal lymphoma presenting as frosted branch angiitis in a patient with diffuse large B-cell lymphoma.

Purpose: To describe the evaluation, diagnosis, and treatment of vitreoretinal lymphoma presenting as frosted branch angiitis in a patient with diffuse large B-cell lymphoma (DLBCL). Observations: A 57-year-old woman with a history of non-Hodgkin lymphoma and recent DLBCL relapse presented with frosted branch angiitis that raised suspicion for an infectious retinitis but was found to be vitreoretinal lymphoma. Conclusions and Importance: This case primarily highlights the importance of considering vitreoretinal lymphoma on the differential diagnosis of etiologies of frosted branch angiitis. Despite suspicion for vitreoretinal lymphoma, it is also important to treat empirically for infectious etiologies of retinitis in cases of frosted branch angiitis. In this case where the diagnosis was ultimately vitreoretinal lymphoma, weekly alternating intravitreal injections of methotrexate and rituximab led to improvement in visual acuity and retinal infiltration.

COMBINED RHEGMATOGENOUS RETINAL AND CHOROIDAL DETACHMENT: A Systematic Review.

PURPOSE: To review the literature on eyes with concurrent rhegmatogenous retinal and choroidal detachment (RRD-CD). METHODS: Several databases were searched for "rhegmatogenous retinal detachment" and "choroidal detachment" through October 2022. All English language primary literature was reviewed. RESULTS: Studies demonstrated that eyes with RRD-CD were very uncommon and had diminished baseline visual acuity (VA) and intraocular pressure (IOP) compared with eyes with RRD only. Although no randomized trials have been performed, pars plana vitrectomy with or without scleral buckle (SB) have reported higher surgical success rates than SB alone. Reattachment rates were affected by age, IOP, adjuvant steroids, and grade of proliferative vitreoretinopathy. CONCLUSION: Low IOP and poor initial VA are salient features of eyes with RRD-CD. Steroids can be useful adjuvants administered safely using several routes including periocular and intravitreal injection. PPV ± SB may result in best surgical outcomes.

NPHP1 FULL DELETION CAUSES NEPHRONOPHTHISIS AND A CONE-ROD DYSTROPHY.

PURPOSE: To describe in detail the structural and functional phenotypes of a patient with cone-rod dystrophy associated with a full deletion of the NPHP1 gene. METHODS: A 30-year-old man with a history of end-stage renal disease presented with progressive vision loss in early adulthood prompting evaluation for retinal disease. Ophthalmic evaluation was performed including visual fields, electroretinography, spectral domain optical coherence tomography and short-wavelength and near-infrared fundus autofluorescence imaging. RESULTS: The visual acuity was 20/60 in each eye. Fundus examination revealed a subtle bull's-eye maculopathy confirmed with fundus autofluorescence. Spectral domain optical coherence tomography demonstrated perifoveal loss of the outer retinal layers with structural preservation further peripherally. Static perimetry confirmed the loss of cone greater than rod sensitivities in a manner that colocalized to structural findings. Electroretinography revealed decreased cone- and rod-mediated responses. Genetic testing confirmed a homozygous whole-gene deletion of the NPHP1 gene. CONCLUSION: NPHP1 -associated retinal degeneration may present as a cone-rod dystrophy in addition to the previously reported rod-predominant phenotypes and can notably be associated with systemic abnormalities, including renal disease. Our work further expands on the growing literature describing the retinal disease associated with systemic ciliopathies.

QUANTITATIVE ASSESSMENT OF AUTOMATED OPTICAL COHERENCE TOMOGRAPHY IMAGE ANALYSIS USING A HOME-BASED DEVICE FOR SELF-MONITORING NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate a prototype home optical coherence tomography device and automated analysis software for detection and quantification of retinal fluid relative to manual human grading in a cohort of patients with neovascular age-related macular degeneration. METHODS: Patients undergoing anti-vascular endothelial growth factor therapy were enrolled in this prospective observational study. In 136 optical coherence tomography scans from 70 patients using the prototype home optical coherence tomography device, fluid segmentation was performed using automated analysis software and compared with manual gradings across all retinal fluid types using receiver-operating characteristic curves. The Dice similarity coefficient was used to assess the accuracy of segmentations, and correlation of fluid areas quantified end point agreement. RESULTS: Fluid detection per B-scan had area under the receiver-operating characteristic curves of 0.95, 0.97, and 0.98 for intraretinal fluid, subretinal fluid, and subretinal pigment epithelium fluid, respectively. On a per volume basis, the values for intraretinal fluid, subretinal fluid, and subretinal pigment epithelium fluid were 0.997, 0.998, and 0.998, respectively. The average Dice similarity coefficient values across all B-scans were 0.64, 0.73, and 0.74, and the coefficients of determination were 0.81, 0.93, and 0.97 for intraretinal fluid, subretinal fluid, and subretinal pigment epithelium fluid, respectively. CONCLUSION: Home optical coherence tomography device images assessed using the automated analysis software showed excellent agreement to manual human grading.

ADULT-ONSET BEST1 -VITELLIFORM DYSTROPHY ASSOCIATED WITH ANGIOID STREAK-LIKE CHANGES IN TWO SIBLINGS.

BACKGROUND/PURPOSE: To describe the association between autosomal dominant Best disease and peripapillary angioid streak-like changes. METHODS: Case report of two siblings. RESULTS: A 76-year-old White man was referred for evaluation of bilateral macular changes and worsening visual distortion over the preceding 2 years. Best-corrected visual acuity measured 20/30 in the right eye and 20/80 in the left eye. Funduscopic examination revealed multifocal yellow lesions in the posterior pole that were hyperautofluorescent on short-wavelength excitation and corresponded with subretinal hyperreflective material on optical coherence tomography. The posterior pole examination was interesting because of the juxtapapillary involvement of the vitelliform lesions and the presence of bilateral peripapillary angioid streak-like changes despite no history of conditions associated with angioid streaks. On further workup, an electrooculogram revealed reduced Arden ratios and a known heterozygous missense mutation in BEST1 (c.903T>G; p .D301E) was found. The patient's 69-year-old younger brother was brought in and found to have a remarkably similar phenotype, including the presence of angioid streak-like changes associated with the same BEST1 mutation. CONCLUSION: These two cases demonstrate the possibility of late-onset multifocal vitelliform disease due to dominantly inherited BEST1 . A consistent phenotype in this family with macular lesions extending into the peripapillary region, associated with angioid streak-like changes, suggests susceptibility of this region to changes in dominant BEST1 -vitelliform macular dystrophy.

UTILITY OF OCULAR ß- d -GLUCAN TESTING IN PATIENTS WITH FUNGAL ENDOPHTHALMITIS.

PURPOSE: To assess the diagnostic utility of (1→3)-ß- d -glucan (BDG) in ocular fluid of patients with fungal endophthalmitis. METHODS: This prospective pilot single-center study evaluated aqueous and vitreous humor BDG levels of suspected fungal endophthalmitis, bacterial endophthalmitis, and noninfectious controls with the standard Fungitell assay and the Fungitell STAT assay. ß- d -Glucan levels were compared using generalized linear models followed by post hoc pairwise comparisons. RESULTS: Seven fungal endophthalmitis, 6 bacterial endophthalmitis, and 17 noninfectious ocular samples were evaluated. Mean aqueous BDG concentrations were 204, 11.0, and 9.6 pg/mL for fungal endophthalmitis, bacterial endophthalmitis, and noninfectious controls, respectively ( P = 0.01, fungal vs. bacterial; P = 0.0005, fungal vs. noninfectious controls). Mean vitreous BDG concentrations were 165, 30.3, and 5.4 pg/mL, respectively ( P = 0.001 for fungal vs. bacterial; P < 0.0001 for fungal vs. noninfectious controls). Mean vitreous BDG index (Fungitell STAT) values were 1.7, 0.4, and 0.3, respectively ( P = 0.001, fungal vs. bacterial; P = 0.0004, fungal vs. noninfectious controls). The Pearson correlation between BDG levels and BDG index was high (correlation coefficient = 0.99, P < 0.001). CONCLUSION: Significantly elevated ocular BDG levels were found in fungal endophthalmitis compared with bacterial endophthalmitis and noninfectious controls. Our study suggests a potential utility for BDG testing in the diagnosis of fungal endophthalmitis, and a larger study is warranted.

VISION-RELATED MALPRACTICE INVOLVING PRISONERS: Analysis of the Westlaw Database.

PURPOSE: To characterize vision-related malpractice litigation involving prisoners. METHODS: Retrospective legal database review using the Westlaw database was performed to identify vision-related malpractice lawsuits involving prisoners in the United States from 1914 to 2020. Main outcomes and measurements were allegations of malpractice, verdicts, and settlements. RESULTS: Sixty-four vision-related malpractice lawsuits involving prisoners were identified. Mean defendant age was 49 years (range, 28-74 years). Fifty-seven percent of the defendants were ophthalmologists and 43% were optometrists. The cases were most commonly from the South and Midwest (n = 19 [30%] for each). Allegations of malpractice included inadequate medical care or treatment refusal (n = 21 [33%]), failure to treat fully leading to continued suffering (n = 18 [28%]), and delay in treatment or referral (n = 17 [27%]). Retina-related diagnoses were most common (n = 18 [28%]). Forty-six (72%) cases were closed, 14 (22%) were open, and four (6.3%) were partially closed. Only two (3.1%) cases were decided in favor of the plaintiff. The most common reason for an unsuccessful suit was lack of deliberate indifference by the eye care professional (n = 21 [46%]). CONCLUSION: The most common reasons for vision-related malpractice brought forth by prisoners were inadequate or incomplete eye care and treatment refusal. Retina was the most commonly involved subspecialty. However, the success rate of these suits was extremely low.

Risk of non-infectious uveitis or myasthenia gravis in patients on checkpoint inhibitors in a large healthcare claims database.

AIM: To determine if checkpoint inhibitors (CPIs) confer an increased risk of non-infectious uveitis or myasthenia gravis (MG) compared to patients on non-checkpoint inhibitor (N-CPI) chemotherapy. METHODS: A retrospective cohort study was performed comparing patients in a large commercial and Medicare advantage database exposed to CPI compared to N-CPI. All patients who initiated a CPI (ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, cemiplimab and durvalumab) were eligible. Date of earliest CPI in the exposure group and N-CPI chemotherapy in the comparator group was considered the index date. Exclusion occurred in both cohorts for any history of uveitis or MG diagnosis and having <1 year in the insurance plan prior to the index date, and <6 months in plan following the index date. Every exposed patient was matched up to 1:10 based on demographics and index year to patients on N-CPI chemotherapy. Multivariate Cox proportional hazards regression modelling was performed. RESULTS: For evaluation of incidence of non-infectious uveitis, 26 (0.3%) of 8678 patients on CPI and 123 (0.2%) of 76 153 N-CPI comparators were found to have non-infectious uveitis. After multivariate analysis, CPIs showed an increased hazard for uveitis compared to N-CPI (HR=2.09; 95% CI 1.36 to 3.22, p=0.001). For the MG analysis, 11 (0.1%) of 9210 patients developed MG in the CPI group and 36 (0.04%) of 80 620 comparators. The CPI cohort had a higher hazard of developing MG (HR=2.60; 95% CI 1.34 to 5.07, p=0.005) compared to controls in multivariate analysis. CONCLUSIONS: Exposure to CPI confers a higher risk for non-infectious uveitis and MG compared to N-CPI chemotherapy.

TRIANGULAR SIGN OF AMALRIC IN INTRAVASCULAR LYMPHOMA.

PURPOSE AND METHODS: To report a case of bilateral ocular ischemia caused by intravascular lymphoma with the presence of bilateral triangular sign of Amalric. RESULTS: A 67-year-old woman was admitted to our hospital for progressive paraplegia and a 6-month history of acute painless vision loss in the right eye. Initial examination showed vision of counting fingers in the right eye and 20/20 in the left eye with normal anterior examination. Fundus examination revealed a likely previous central retinal artery occlusion in the right eye with pale nerve and attenuated vessels. Both fundi had triangular regions of pigmentary change known as the triangular sign of Amalric, indicative of choroidal ischemia. However, the left eye was asymptomatic. Neuroimaging revealed multifocal enhancing lesions throughout the central nervous system of unclear etiology. An extensive neurologic and systemic workup was unrevealing, including a brain biopsy, and empiric treatment for an unspecified inflammatory condition with intravenous corticosteroids was initiated. During her hospitalization, she developed acute painless vision loss in the left eye, and examination showed no light perception vision in both eyes with signs of acute retinal and choroidal ischemia in the left eye. A subsequent brain biopsy revealed intravascular lymphoma. CONCLUSION: Triangular pigmentary changes indicate choroidal ischemia and can be seen in many conditions. This patient presented with the triangular sign of Amalric in both eyes, including her asymptomatic left eye. Intravascular lymphoma should be considered in cases of concomitant inflammatory brain lesions and chorioretinal ischemia.

Rhegmatogenous Retinal Detachment with concurrent Choroidal Detachment and Macular Hole Formation after Uncomplicated Cataract Extraction and Intraocular Lens Implantation - A Case Report and Review of Literature.

PURPOSE: To describe a case of concurrent rhegmatogenous retinal detachment, choroidal detachment, and macular hole (RRD-CD-MH) formation in a patient after uncomplicated cataract extraction and intraocular lens implantation (CEIOL). In addition, we summarize the previously reported cases of RRD-CD-MH in the literature. METHODS: Interventional case report and literature review. RESULTS: A 71-year-old white man without relevant past medical or ocular history underwent an uncomplicated CEIOL. He presented three weeks later with counting fingers vision and intraocular pressure (IOP) of 5 mmHg. On dilated fundus examination, multiple superior tears and total RRD with a serous CD was evident. Intraoperatively, a full-thickness MH was identified. The patient underwent routine RRD and MH repair, with instillation of 1000 centistoke silicone oil (SiO). The retina successfully re-attached, the CD resolved, and the IOP normalized; however, the MH did not initially close. The SiO was removed ∼4 months later and, while the MH remained open, the patient's vision improved to 20/80. Approximately three years after the surgical repair, the MH closed spontaneously, and the vision remained at 20/80. CONCLUSION: Our patient developed an RRD-CD-MH post-uncomplicated CEIOL. The MH displayed delayed closure. The vision improved after surgical repair, and remained stable in the long-term.

CLINICAL UTILITY OF BETA-D-GLUCAN TESTING FOR ENDOGENOUS FUNGAL CHORIORETINITIS OR ENDOPHTHALMITIS.

PURPOSE: To evaluate serum beta-D-glucan (BDG) as a biomarker for endogenous fungal eye infection. METHODS: Retrospective case-control study of 88 patients with a BDG test and eye examination at UPenn (2013-2018). Cases had endogenous fungal chorioretinitis or endophthalmitis diagnosed by eye examination and confirmed with positive culture; controls were without these fungal eye findings. Charts were reviewed for BDG values, blood/vitreous cultures, and eye examinations. Outcomes were BDG sensitivity, specificity, positive predictive value, and negative predictive value for fungal chorioretinitis or endophthalmitis, using prespecified BDG cut-off points of ≥80, ≥250, and ≥500 pg/mL as test positive. RESULTS: Cases included six chorioretinitis and four endophthalmitis patients. Controls included 78 patients without chorioretinitis or endophthalmitis. Defining BDG ≥80 pg/mL as test positive, the BDG sensitivity (95% confidence interval) was 66.7% (22.3%-95.7%) for chorioretinitis and 100% (39.8%-100%) for endophthalmitis. The specificity was 74.4% (63.2%-83.6%) when BDG values ≥80 pg/mL were test positive, and 85.9% (76.2%-92.7%) when values ≥250 pg/mL were test positive. For a 1% endophthalmitis prevalence and BDG cut-off value of ≥80 pg/mL, the positive predictive value was 3.8% (2.4%-5.2%) and negative predictive value was 100% (99.1%-100%). CONCLUSION: For endogenous fungal endophthalmitis, BDG's sensitivity and specificity seem good and the negative predictive value is high; a larger ophthalmic study is indicated.