Comparative analysis of in-silico tools in identifying pathogenic variants in dominant inherited retinal diseases.

Inherited retinal diseases (IRDs) are a group of rare genetic eye conditions that cause blindness. Despite progress in identifying genes associated with IRDs, improvements are necessary for classifying rare autosomal dominant (AD) disorders. AD diseases are highly heterogenous, with causal variants being restricted to specific amino acid changes within certain protein domains, making AD conditions difficult to classify. Here, we aim to determine the top-performing in-silico tools for predicting the pathogenicity of AD IRD variants. We annotated variants from ClinVar and benchmarked 39 variant classifier tools on IRD genes, split by inheritance pattern. Using area-under-the-curve (AUC) analysis, we determined the top-performing tools and defined thresholds for variant pathogenicity. Top-performing tools were assessed using genome sequencing on a cohort of participants with IRDs of unknown etiology. MutScore achieved the highest accuracy within AD genes, yielding an AUC of 0.969. When filtering for AD gain-of-function and dominant negative variants, BayesDel had the highest accuracy with an AUC of 0.997. Five participants with variants in NR2E3, RHO, GUCA1A, and GUCY2D were confirmed to have dominantly inherited disease based on pedigree, phenotype, and segregation analysis. We identified two uncharacterized variants in GUCA1A (c.428T>A, p.Ile143Thr) and RHO (c.631C>G, p.His211Asp) in three participants. Our findings support using a multi-classifier approach comprised of new missense classifier tools to identify pathogenic variants in participants with AD IRDs. Our results provide a foundation for improved genetic diagnosis for people with IRDs.

Endoscopy-assisted pars plana vitrectomy in retinal detachments associated with anterior proliferative vitreoretinopathy and epiciliary membranes.

BACKGROUND: Proliferative vitreoretinopathy (PVR) is the leading cause of recurrent retinal detachment. Anterior PVR can contribute to recurrent retinal detachment and is often difficult to remove during conventional pars plana vitrectomy. The purpose of this study is to report surgical outcomes of single endoscopy-assisted pars plana vitrectomy (E-PPV) in patients with tractional retinal detachments associated with anterior proliferative vitreoretinopathy and epiciliary membranes. METHODS: Retrospective review of E-PPV between 2017 and 2021 at a tertiary referral center. Inclusion criteria involved adult patients who underwent E-PPV for tractional retinal detachment with anterior PVR and epiciliary membranes. Data collection included patients' demographics, ophthalmic exam findings, and surgical outcomes. A series of independent sample tests of proportion were conducted using a p-value of 0.05 as the threshold for statistical significance. RESULTS: Eighteen out of 55 patients who underwent E-PPV met the inclusion criteria. There were six females (33%) and 12 males (p-value = 0.096). Age ranged between 27 and 82 years old (mean age 52.1 ± 17.3 years). Nine patients (50%) had a history of ipsilateral retinal detachment repair. Single E-PPV success rate was 100% after three months, and 94.4% at the latest follow up visit. Recurrent retinal detachment with posterior PVR occurred in one patient four months after surgery. Cataract progressed in 57% (8/14) of phakic patients, with 63% (5/8) undergoing cataract extraction surgery within the first postoperative year. CONCLUSION: E-PPV enabled epiciliary membrane and anterior PVR visualization and removal. The single E-PPV success rate remained high at the latest follow up visit. E-PPV enabled the preservation of the phakic lens in all study patients. Larger prospective studies are needed on the role of E-PPV in retina surgeries.

Mycobacterium chimaera chorioretinitis preceding central nervous system lesions: a case report and review of the literature.

BACKGROUND: Mycobacterium chimaera ocular infection is a rare disease that is linked to bypass devices used during cardiothoracic surgeries. Reported cases in the literature of ocular involvement preceding CNS involvement are based on clinical exam with no neuroimaging. Here we present a case of M. chimaera ocular infection with no CNS M. chimaera lesions on brain magnetic resonance imaging (MRI). CASE PRESENTATION: A 59-year-old female presented with altered mental status and blurred vision in February 2021. Her past medical history was significant for aortic valve replacement and ascending aortic aneurysm repair in 2017 complicated by known M. chimaera infection. She had been receiving azithromycin, ethambutol, rifampin, and amikacin as systemic anti-mycobacterium treatment. Her dilated fundus exam showed numerous yellow placoid circular lesions scattered throughout the macula and peripheral retina in both eyes with associated vitritis. Systemic workup, including brain MRI showed no acute infectious lesions. Her infections workup was unremarkable except for a positive toxoplasma IgM, for which she was treated with sulfamethoxazole/trimethoprim. One month later, a head computed tomography showed new numerous scattered round foci of hyperdensity throughout the cerebrum and brainstem thought to be foci of M. chimaera infection. Clofazimine was added per culture and sensitivity. MRI brain 1 month later showed mild decrease in conspicuity and number of these intensities while on anti-mycobacterium treatment. Her cognition had improved at that time as well. She was seen in retina clinic 2 months later where her exam showed similar retinal lesions with no associated vitritis or anterior chamber cell in bilateral eyes, suggesting a lack of active infection. Optical coherence tomography macula showed parafoveal cystoid macular edema bilaterally. She was started on steroidal and non-steroidal anti-inflammatory eye drops. CONCLUSIONS: To the best of our knowledge, this is the first case in the literature to report M. chimaera chorioretinitis with concomitant negative neuroimaging. Chorioretinal M. chimaera lesions should motivate high suspicion of CNS involvement prompting early neurological work up.

NONCONFOCAL ULTRA-WIDEFIELD SCANNING LASER OPHTHALMOSCOPY: Polarization Artifacts and Diabetic Macular Edema.

PURPOSE: Bowtie-shaped polarization artifacts are often present in nonconfocal ultra-widefield scanning laser ophthalmoscope (SLO) images. We studied these artifacts and evaluated their potential value as clinical biomarkers in screening for center-involving diabetic macular edema (DME). METHODS: We performed a retrospective, observational, cohort study on 78 diabetic adult patients (143 eyes) who had spectral domain optical coherence tomography and nonmydriatic nonconfocal ultra-widefield SLO testing on the same day. Scanning laser ophthalmoscope green-only (532 nm), red-only (635 nm), and composite pseudocolor (532 plus 635 nm) images were examined for the presence of a foveal bowtie polarization artifact. RESULTS: Polarization artifacts were absent in all but one eye with center-involving DME (32 of 33 eyes). Polarization artifacts were also absent in many eyes without center-involving DME (49 of 110 eyes in pseudocolor images). As clinical biomarkers of center-involving DME, artifact absence has high specificity (99, 100, and 98% for green, red, and pseudocolor images, respectively) but poor sensitivity (49, 31, and 40% for green, red, and pseudocolor images, respectively). CONCLUSION: Foveal bowtie-shaped polarization artifacts occur routinely in nonconfocal ultra-widefield SLO images. Their presence indicates preserved foveal Henle fiber layer structure. Contemporary nonconfocal ultra-widefield SLO images lack the sensitivity for their bowtie artifacts to serve as reliable biomarkers in screening for center-involving DME.

Bisphosphonate-induced orbital inflammation in a patient on chronic immunosuppressive therapy.

BACKGROUND: To report a case of orbital inflammation after bisphosphonate infusion in a patient who was already receiving immunosuppressive therapy. CASE PRESENTATION: A 56-year-old woman presented to the ophthalmology clinic with acute onset of right eye pain 24 h after receiving her first Zolendronic acid infusion. She has a past medical history of chronic inflammatory demyelinating polyneuropathy, Sjogren's syndrome, and systemic lupus erythematosus that have been controlled with immunosuppressive therapy for three years. Clinical ophthalmic exam and MRI studies were significant for right orbital inflammation. The patient was started on oral prednisone with rapid resolution of symptoms. CONCLUSIONS: This is the first case report of a patient receiving chronic immunosuppressive therapy to develop orbital inflammation after Zoledronic acid infusion. In addition, it demonstrates that corticosteroids can be an effective first line therapy in treating orbital inflammation in similar patients. Physicians should be aware of this rare but serious potential side effect of bisphosphonates, and have bisphosphonate-related orbital inflammation on their differential for proper initiation of treatment.

Leveraging splice-affecting variant predictors and a minigene validation system to identify Mendelian disease-causing variants among exon-captured variants of uncertain significance.

The genetic heterogeneity of Mendelian disorders results in a significant proportion of patients that are unable to be assigned a confident molecular diagnosis after conventional exon sequencing and variant interpretation. Here, we evaluated how many patients with an inherited retinal disease (IRD) have variants of uncertain significance (VUS) that are disrupting splicing in a known IRD gene by means other than affecting the canonical dinucleotide splice site. Three in silico splice-affecting variant predictors were leveraged to annotate and prioritize variants for splicing functional validation. An in vitro minigene system was used to assay each variant's effect on splicing. Starting with 745 IRD patients lacking a confident molecular diagnosis, we validated 23 VUS as splicing variants that likely explain disease in 26 patients. Using our results, we optimized in silico score cutoffs to guide future variant interpretation. Variants that alter base pairs other than the canonical GT-AG dinucleotide are often not considered for their potential effect on RNA splicing but in silico tools and a minigene system can be utilized for the prioritization and validation of such splice-disrupting variants. These variants can be overlooked causes of human disease but can be identified using conventional exon sequencing with proper interpretation guidelines.

Catheter-guided suprachoroidal buckling of rhegmatogenous retinal detachments secondary to peripheral retinal breaks.

PURPOSE: To evaluate functional and anatomic outcomes of eyes undergoing suprachoroidal buckling (SCB) using a specially designed catheter for the management of rhegmatogenous retinal detachment (RRD) secondary to peripheral retinal breaks. METHODS: Retrospective cohort study of 62 eyes of 62 patients. Subjects underwent SCB for the management of RRD secondary to single or multiple retinal breaks. Suprachoroidal indentation was achieved through the introduction of viscoelastic material in the suprachoroidal space overlying the break using an illuminated, 450 µm-wide, flex-tip catheter. This allowed for the creation of a suprachoroidal dome and chorio-retinal apposition. Forty-seven eyes (80 %) underwent SCB alone, while 15 eyes (20 %) were combined with 25-G pars-plana vitrectomy. Cryopexy and laserpexy were used in 38 (61 %) and 24 of eyes (39 %) respectively. RESULTS: Mean pre-operative best-corrected visual acuity (BCVA) improved from logMAR 0.82 (20/132) to 0.22 (20/33) (p < 0.0001). The single surgery reattachment rate was 92 % (57/62.) Final retinal reattachment was achieved in all eyes (100 %). No significant difference was observed in single-surgery anatomic success rates when stratified by lens status, macular involvement, or break location. There were no major intra- or post-operative complications. CONCLUSION: Suprachoroidal buckling using a special-design, flexible catheter is a safe and effective procedure for the management of RRD secondary to peripheral retinal breaks.

Oral 9-cis retinoid for childhood blindness due to Leber congenital amaurosis caused by RPE65 or LRAT mutations: an open-label phase 1b trial.

BACKGROUND: Leber congenital amaurosis, caused by mutations in RPE65 and LRAT, is a severe form of inherited retinal degeneration leading to blindness. We aimed to assess replacement of the missing chromophore 11-cis retinal with oral QLT091001 (synthetic 9-cis-retinyl acetate) in these patients. METHODS: In our open-label, prospective, phase 1b trial, we enrolled patients (aged ≥6 years) with Leber congenital amaurosis and RPE65 or LRAT mutations at McGill University's Montreal Children's Hospital. Patients received 7 days of oral QLT091001 (10-40 mg/m(2) per day). We assessed patients at baseline and days 7, 9, 14, and 30, and then 2 months and every 2 months thereafter for up to 2·2 years for safety outcomes and visual function endpoints including Goldmann visual fields (GVF), visual acuity, and functional MRI assessment. We regarded patients as having an improvement in vision if we noted at least a 20% improvement in retinal area on GVF compared with baseline or a visual acuity improvement of five or more letters compared with baseline in two consecutive study visits (or any improvement from no vision at baseline). This study is registered with ClinicalTrials.gov, number NCT01014052. FINDINGS: Between December, 2009, and June, 2011, we enrolled and treated 14 patients aged 6-38 years who were followed up until March, 2012. Ten (71%) of 14 patients had an improvement in GVF areas (mean increase in retinal area of 28-683%). Six (43%) patients had an improvement in visual acuity (mean increase of 2-30 letters). Self-reported or parent-reported improvements in activities of daily living supported these findings. After 2 years, 11 (79%) patients had returned to their baseline GVF retinal area and ten (71%) had returned to baseline visual acuity letter values. Thus, three (21%) patients had a sustained GVF response and four (30%) had a sustained visual acuity response. Four patients had functional MRI scans, which correlated with visual response or absence of response to treatment. No serious adverse events occurred, although we noted transient headaches (11 patients), photophobia (11 patients), reduction in serum HDL concentrations (four patients), and increases in serum triglycerides (eight patients) and aspartate aminotransferase concentrations (two patients). INTERPRETATION: Non-invasive oral QLT091001 therapy is well tolerated, and can rapidly improve visual function in some patients with Leber congenital amaurosis and RPE65 and LRAT mutations. FUNDING: QLT, Foundation Fighting Blindness Canada, CIHR, FRSQ, Reseau Vision.

Expression of PRPF31 and TFPT: regulation in health and retinal disease.

PRPF31, a gene located at chromosome 19q13.4, encodes the ubiquitous splicing factor PRPF31. The gene lies in a head-to-head arrangement with TFPT, a poorly characterized gene with a role in cellular apoptosis. Mutations in PRPF31 have been implicated in autosomal dominant retinitis pigmentosa (adRP), a frequent and important cause of blindness worldwide. Disease associated with PRPF31 mutations is unusual, in that there is often non-penetrance of the disease phenotype in affected families, caused by differential expression of PRPF31. This study aimed to characterize the basic promoter elements of PRPF31 and TFPT. Luciferase reporter constructs were made, using genomic DNA from an asymptomatic individual with a heterozygous deletion of the entire putative promoter region. Fragments were tested by the dual-luciferase reporter assay in HeLa and RPE-1 cell lines. A comparison was made between the promoter regions of symptomatic and asymptomatic mutation-carrying individuals. A patient (CAN493) with adRP was identified, harbouring a regulatory region mutation; both alleles were assayed by the dual-luciferase reporter assay. Luciferase assays led to the identification of core promoters for both PRPF31 and TFPT; despite their shared gene architecture, the two genes appear to be controlled by slightly different regulatory regions. One functional polymorphism was identified in the PRPF31 promoter that increased transcriptional activation. The change was not, however, consistent with the observed symptomatic-asymptomatic phenotypes in a family affected by PRPF31-adRP. Analysis of the mutant promoter fragment from CAN493 showed a >50% reduction in promoter activity, suggesting a disease mechanism of functional haploinsufficiency-the first report of this disease mechanism in adRP.

Unilateral Episcleritis Following COVID-19 Booster Vaccination of a Crohn's Disease Patient: A Case Report and Review of the Literature.

Purpose: The Coronavirus Disease 2019 (COVID-19) pandemic spurred vaccine development and resulted in the development of the novel mRNA COVID-19 vaccine and with it, a growing public concern of vaccine side effects. There are reports of ocular inflammatory processes such as episcleritis being possible side effects of COVID-19 vaccination. Here we reported the first case of unilateral episcleritis in a Crohn's disease patient following her third mRNA COVID-19 vaccination booster shot. Patient and Methods: A 27-year-old female presented with a 1-day history of right eye redness, itching, and burning. Patient reported developing these symptoms within 3-4 hours after vaccination. Her past medical history was relevant for Crohn's disease. Ophthalmic examination revealed right 2+ conjunctival injection that blanched with phenylephrine drops. Otherwise, her ophthalmic exam was unremarkable. The patient was started on artificial tears and ibuprofen 200 mg three times daily for one week. After one week all symptoms resolved, and ophthalmic examination was back to baseline. Conclusion: This is the first case in the literature of ophthalmic side effects in a Crohn's disease patient after the third mRNA COVID-19 booster. Patients with Crohn's disease may respond differently to booster vaccination. This case report may help healthcare providers when counselling Crohn's disease patients about future COVID-19 mRNA vaccine side effects.

Bilateral Cystoid Macular Edema with Zanubrutinib Therapy: A Case Report.

We present a patient with recurrent mantle cell lymphoma (MCL) who was treated with zanubrutinib, a Bruton's tyrosine kinase inhibitor. He subsequently developed bilateral cystoid macular edema (CME) in both eyes. This is the first report of CME in a patient with MCL who was treated with zanubrutinib. CME was refractory to topical corticosteroid therapy, but sub-Tenon's steroid injections and holding off zanubrutinib managed to decrease the CME. Treatment managed to prevent further vision loss but did not restore lost vision. The prompt ophthalmic exam is recommended for patients on zanubrutinib with decreased vision.

Treatment of serpiginous choroiditis with sub-tenon triamcinolone in conjunction with systemic steroids case report.

PURPOSE: To report two cases of serpiginous choroiditis which were treated with sub-Tenon's triamcinolone in conjunction with systemic steroids to control acute and chronic disease progression. Increased success of disease remission has been postulated for sub-Tenon's triamcinolone therapy in conjunct with systemic steroids. METHODS: Retrospective chart review of two serpiginous choroiditis patients who presented at an eye center. Both patients received sub-Tenon's triamcinolone and systemic steroids. Visual acuity and disease course are reported. RESULTS: Both cases of serpiginous choroiditis received sub-Tenon's triamcinolone on presentation and were hospitalized for intravenous corticosteroids and systemic work up. The first patient had been on oral corticosteroids before presentation. Both patients reported same day visual improvement after sub-Tenon's triamcinolone was administered. CONCLUSIONS: These two case reports describe unique clinical scenarios in which sub-Tenon's triamcinolone was used in both the acute and chronic phases of serpiginous choroiditis. Local steroid therapy can be a useful adjunctive therapy when systemic steroids are delayed, contraindicated or intolerable.

Endoscopic Pars Plana Vitrectomy in Patients With Open-Globe Injury and Corneal Opacity.

Purpose: To determine the 1-year outcomes of endoscopic pars plana vitrectomy (EPPV) and its impact on the corneal transplantation rate in patients with open-globe injury (OGI) and corneal opacity. Methods: This retrospective cohort study collected data between December 2018 and August 2021. All EPPVs were performed at a level I trauma center. Inclusion criteria were adult patients with a history of OGI complicated by corneal opacification that prevented fundus visualization. The main outcome measures were the rate of successful retinal reattachment, final visual acuity (VA), and number of patients who had penetrating keratoplasty (PKP) within 1 year of the OGI. Results: Ten patients (3 women; 7 men) with a mean age of 63.4 ± 22.7 years (SD) met the inclusion criteria. The indications for EPPV were intraocular foreign bodies in 2 patients, dense vitreous hemorrhage in 3 patients (1 with a retinal tear; 1 with a choroidal hemorrhage), and retinal detachment in 5 patients. The final VA ranged from 20/40 to no light perception. All 4 repaired detachments remained attached after 1 year. Corneal opacity was treated with PKP in 3 patients. Conclusions: Results indicate EPPV can be a useful tool to treat posterior segment pathology in patients with a recent OGI and corneal opacity. EPPV can help address posterior segment disease and postpone corneal transplantation until the visual potential can be fully determined. Larger prospective studies are needed.

Optic inversion of scleral-fixated intraocular lens after vitrectomy with fluid-air exchange: case series and review of the literature.

Lens dislocation is a significant complication after cataract surgery. Scleral fixation of 3-piece intraocular lens provides favorable visual outcome and can spare patients the need for lens exchange. Two patients presented with dislocated 3-piece lenses implanted over 10 years earlier. Both patients underwent pars plana vitrectomy and dropped lens rescue with scleral fixation. Postoperatively, the lens optic was found flipped nearly 90° at the optic-haptic junctions secondary to fluid-air exchange performed during vitrectomy. Both patients underwent intraocular lens exchange with a four point sclera fixated lens. Our study found that air tamponade is better avoided during rescue of old dislocated 3-piece lens implants. Intraocular lens exchange is preferred, when possible, to avoid complications associated with old dislocated lenses. Larger studies are needed to determine the effect of time on dislocated lens implants materials.

Unilateral COVID-19-associated vasculitic central retinal vein occlusion: phlebitis with subhyaloid, intraretinal and subretinal hemorrhages.

PURPOSE: To describe unilateral vasculitic central retinal vein occlusion (CRVO) in a young adult whose vision problems preceding system symptoms of COVID-19 infection. METHODS: Observational clinical case report. RESULTS: A 39-year-old immunocompetent male without prior ocular disease presented for vitreoretinal care complaining of decreasing vision in his right eye for two weeks. Headaches, pharyngitis and coughing began four days after his visual symptoms. COVID-19 testing was negative prior to initial vitreoretinal evaluation and positive afterward. Dilated and tortuous major retinal veins in his right eye had prominent perivascular sheathing. A large subhyaloid hemorrhage spanned the macula. Subretinal hemorrhages were present in areas of sheathing and diffuse nerve fiber layer hemorrhages were arrayed in the distribution of the radial peripapillary capillary plexus. Laboratory tests for inflammatory diseases were negative. The patient was hospitalized for COVID-19 pneumonia a few days after his initial vitreoretinal evaluation. Pars plana vitrectomy was performed for persistent subhyaloid hemorrhage eight weeks after his hospitalization. The visual acuity in the patient's right eye improved from CF to 20/30 post-operatively. CONCLUSION: The patient's findings are consistent with an atypical CRVO which we hypothesize to be of vasculitic origin because of prominent associated retinal phlebitis and venous sheathing. Concomitant subhyaloid, nerve fiber layer and subretinal hemorrhages involved the superficial and deep retinal vascular complexes. The patient's COVID-19-related hospitalization and systemic management delayed surgical management of his subhyaloid hemorrhages but a good visual result was achieved despite persistence of macular preretinal blood for three months.

Prophylactic Laser Treatment Posterior to Pars Plana Vitrectomy Sclerotomy Wounds During Macular Surgery.

Introduction: Sclerotomy related retinal breaks (SRRBs) are a risk factor for postoperative retinal detachment (RD). Endolaser posterior to sclerotomy wounds decreased the risk of SRRBs after 20G pars plana vitrectomy (PPV) for macular disease. However, similar data do not exist for 25G and 23G wounds. Methods: A retrospective cohort study of patients after 23G and 25G PPV for macular pathology was conducted between August 2017 and August 2020. The primary outcome was the postoperative rate of SRRBs or RDs. The secondary outcome was the postoperative rate of pupillary dysfunction and neurotrophic keratopathy. All participants had a minimum postoperative follow-up of one year. Results: One hundred seventeen patients were included in the study (62 in the laser group and 55 in the control group). Mean age was 65.4 ± 11.3 years (56.4% female and 43.6% male). Most of the laser group underwent 23G PPV (90%) while most of the control group underwent 25G PPV (96%). One patient in the control group developed RD secondary to a SRRB. No SRRBs or RDs developed in the laser group. None of the secondary outcomes developed in either group after one year. Conclusions: To the best of the authors' knowledge, this is the first report in the literature on prophylactic laser posterior to small gauge sclerotomies (25G and 23G) during macular surgery. Laser treatment posterior to small gauge sclerotomies (25G and 23G) had a similar incidence of SRRBs as with 20G sclerotomies. Larger prospective studies are needed to further understand the role of laser in lowering SRRB risk.

Uveo-meningeal syndrome secondary to Herpes Simplex Virus related acute retinal necrosis.

PURPOSE: To present a rare case of uveo-meningeal syndrome secondary to herpes simplex virus (HSV-1) in a patient with acute retinal necrosis. OBSERVATIONS: A 49-year-old female with a past medical history of herpes simplex encephalitis 18 years prior presented with a 3-day history of right sided headache and decreased vision of the right eye. Her visual acuity was 20/30 in the right eye and 20/20 in the left eye. Clinical examination revealed right relative afferent pupillary defect, panuveitis, and retinal necrosis. Examination of the left eye was unremarkable. Cerebral spinal fluid (CSF) analysis by polymerase chain reaction (PCR) was negative for herpes simplex virus 1 (HSV-1) but did reveal pleocytosis consistent with meningitis. The patient was admitted and empirically treated with intravenous acyclovir (10 mg/kg every 8 hours) and systemic steroids. Topical steroids and cycloplegia were also started. Magnetic resonance imaging revealed no leptomeningeal, pachymeningeal, or parenchymal enhancement. Systemic autoimmune and infectious workup were unremarkable. Based on clinical exam findings and negative PCR results, an anterior chamber tap was performed with aqueous fluid PCR testing which revealed 71,000 copies of HSV-1. A repeat lumbar puncture was performed on day three of admission and revealed a decrease in pleocytosis after initiation of acyclovir therapy and remained negative for HSV on PCR testing. She was discharged home on intravenous acyclovir, topical steroids, and topical cycloplegics. Her retinal necrotic lesions continued to regress and her headaches continued to improve. CONCLUSIONS AND IMPORTANCE: Uveo-meningeal syndromes are a rare clinical entity that involve the uvea, retina, and meninges. This case highlights the importance of aqueous fluid PCR testing despite negative CSF PCR, as it may hasten treatment with antiviral therapies to preserve vision and limit neurologic sequelae.

MINIMAL INVASIVE DRAINAGE TECHNIQUE FOR LARGE EXPANDING SUBRETINAL GAS BUBBLE.

PURPOSE: To report a minimally invasive drainage technique for large expanding subretinal gas bubble and conduct a review of the literature. METHODS: Case report, with schematic diagrams and multimodal imaging including fundus photography and spectral domain optical coherence tomography. Controlled drainage of large subretinal gas bubble using a 30-gauge needle introduced through cryotherapy-treated area in office-based setting. RESULTS: Forty-year-old male patient presented with bullous rhegmatogenous retinal detachment and had gas inadvertently injected into the subretinal space during cryo-pneumatic retinopexy. After successful drainage of subretinal gas in clinic, 0.3cc of perfluoropropane (C3F8) gas was injected in different quadrants near the attached retina. The macula remained attached on immediate fundus examination. The gas bubbles of fish eggs coalesced into a single large bubble within 1 week. Spectral domain optical coherence tomography showed unremarkable foveal scans. After 45 days, the gas bubble completely disappeared, the retina remained attached, and vision in the treated eye was 20/20. CONCLUSION: To the best of our knowledge, this is the first case report of a large expanding gas bubble injected into the subretinal spaces being drained successfully by the described minimal invasive technique. Although it may offer a possible office-based approach to a rare complication, it is generally recommended that surgeons capable of dealing with its possible complications may attempt such technique when immediate vitrectomy is not accessible.

Unilateral retinopathy post perilesional interferon α2b injections for ocular surface squamous cell carcinoma.

PURPOSE: To describe the clinical course of a patient presenting with unilateral retinopathy after perilesional interferon alpha injections for treatment of ocular surface squamous cell carcinoma. OBSERVATIONS: A patient, who was being treated with interferon alpha for ocular squamous cell carcinoma, presented with new onset decreased vision in her left eye. Upon examination, she was found to have cotton wool spots and retinal hemorrhages in the affected eye. CONCLUSIONS AND IMPORTANCE: Retinopathy is a well-documented side effect of systemic usage of interferon alpha. However, retinopathy has not been well discussed in the scenario of perilesional injections of interferon. It is important for clinicians to monitor for such pathology when using interferon alpha not only systemically, but also locally.