Acute macular neuroretinopathy associated with intravitreal anti-VEGF injection: A case report.

Purpose: to report a case of acute macular neuroretinopathy occurring after intravitreal aflibercept injection for macular edema due to CRVO. Observations: Two days after Aflibercept intravitreal injection, the patient developed vision loss associated with a central scotoma. Optical coherence tomography showed a hyperreflective band at the level of the outer nuclear/outer plexiform layer corresponding to the patient's scotoma, ruling in the diagnosis of acute macular neuroretinopahty. Even though the OCT abnormalities resolved spontaneously, only partial resolution of the scotoma was observed 4 months later. Conclusions and importance: Acute macular neuroretinopathy might be associated with intravitreal anti-VEGF injection.

Adult-onset bestrophinopathy mistaken as central serous chorioretinopathy.

PURPOSE: To highlight cases of adult-onset bestrophinopathy mistaken as central serous chorioretinopathy (CSCR). METHODS: Retrospective case series. RESULTS: Two unrelated adult males (54 years old and 43 years old) with serous macular detachments were managed as CSCR. One had been treated with intraocular injections and oral mineralcorticoid inhibitors. Independently, each had an 8-year-old son who presented with classic Best disease, which raised suspicion for bestrophinopathy in their fathers. Bestrophin sequencing confirmed each son to be heterozygous for a pathogenic variant, and targeted testing confirmed each respective father to harbor the same heterozygous pathogenic variant as his son. Electro-oculography of the first father-son pair confirmed decreased Arden ratios. Review of multimodal imaging of the adult patients revealed a hyper-autofluorescent edge surrounding a serous macular detachment by short-wave autofluorescence and shaggy photoreceptors on the overlying edge of serous detachments by optical coherence tomography. DISCUSSION: Adult-onset bestrophinopathy can be mistaken as CSCR. Multimodal imaging findings, examination of potentially affected family members, electrophysiology, and genetic testing facilitate the correct diagnosis.

Adjunctive Intravitreal Triamcinolone Acetonide for Exudative Retinal Detachment in Coats Disease.

Purpose: This work aims to assess the value of intravitreal triamcinolone acetonide (IVTA) as an adjunctive therapy in advanced Coats disease with exudative retinal detachment (ERD). Methods: A retrospective review was conducted of patients with Coats disease stage 3 or higher who received IVTA to decrease subretinal fluid (SRF), facilitate retinal ablative therapy, and avoid surgical drainage. Primary outcomes were SRF resolution and avoidance of surgical SRF drainage. Results: Seventeen eyes of 17 patients (mean, [SD] age, 3.9 [3.4] years) met the inclusion criteria. ERD configuration was bullous in 7 and shallow in 10 eyes. Following a single IVTA injection, ablative therapy was achieved after a mean (SD) of 2.1 (3.0) weeks. Complete SRF resolution was observed in 13 eyes (76.4%) after a mean of 1.3 IVTA injections and a mean of 2 (SD, 1.27) laser sessions, and none of these eyes required SRF drainage up to last follow-up (mean [SD], 50.5 [26.24] months). In 4 eyes with bullous ERD at presentation, SRF persisted (P = .015) despite additional measures including surgical drainage. Final visual acuity ranged from 20/100 to no light perception. Cataract developed in 12 of the 17 eyes (70.5%). None developed an increase in intraocular pressure at final follow-up. Conclusions: IVTA injection can be a helpful adjunctive modality to address SRF in advanced Coats disease. It may obviate the need to surgically drain SRF to effectively treat the condition, particularly when the ERD is not highly bullous.

Association of Ocular Adverse Events With Inactivated COVID-19 Vaccination in Patients in Abu Dhabi.

Importance: As vaccinations against COVID-19 continue, potential ocular adverse events should be reported in detail to increase awareness among the medical community, although typically, a causal relationship cannot be established definitively. Objective: To describe ocular adverse events that occur soon after receiving an inactivated COVID-19 vaccination (Sinopharm). Design, Setting, and Participants: This case series took place from September 2020 to January 2021 at Cleveland Clinic Abu Dhabi, a tertiary referral center. Patients who reported ocular adverse events and presented within 15 days from the first of 2 doses of an inactivated COVID-19 vaccine were analyzed. Main Outcomes and Measures: Each patient underwent Snellen best-corrected visual acuity that was then converted to logMAR, applanation tonometry, and biomicroscopic examination with indirect ophthalmoscopy. Color fundus photography was obtained with a conventional 9-field fundus photography camera or with a widefield fundus photography system. Optical coherence tomography and optical coherence tomographic angiography images were obtained. Sex, race, age, and clinical data were self-reported. Results: Nine eyes of 7 patients (3 male individuals) presenting with ocular complaints following COVID-19 vaccine were included in the study. The mean (SD) age was 41.4 (9.3) years (range, 30-55 years); the mean best-corrected visual acuity was 0.23 logMAR (range, 0-1 logMAR; approximate Snellen equivalent, 20/32). The mean time of ocular adverse event manifestations was 5.2 days (range, 1-10 days). One patient was diagnosed with episcleritis, 2 with anterior scleritis, 2 with acute macular neuroretinopathy, 1 with paracentral acute middle maculopathy, and 1 with subretinal fluid. Conclusions and Relevance: In this case series study of 7 patients, the timing of transient and ocular complications 5.2 days after vaccination with an inactivated COVID-19 vaccine supported an association with the ocular findings, but a causal relationship cannot be established from this study design.

Focal Scleral Nodule: A New Name for Solitary Idiopathic Choroiditis and Unifocal Helioid Choroiditis.

PURPOSE: To evaluate multimodal imaging findings of solitary idiopathic choroiditis (SIC; also known as unifocal helioid choroiditis) to clarify its origin, anatomic location, and natural course. DESIGN: Multicenter retrospective observational case series. PARTICIPANTS: Sixty-three patients with SIC in 1 eye. METHODS: Demographic and clinical data were collected. Multimodal imaging included color fundus photography, OCT (including swept-source OCT), OCT angiography (OCTA), fundus autofluorescence, fluorescein and indocyanine green angiography, and B-scan ultrasonography. MAIN OUTCOME MEASURES: Standardized grading of imaging features. RESULTS: Mean age at presentation was 56 ± 15 years (range, 12-83 years). Mean follow-up duration in 39 patients was 39 ± 55 months (range, 1 month-25 years). The lesions measured a mean of 2.4 × 2.1 mm in basal diameter, were located inferior (64%) or nasal to the optic disc, and appeared yellow (53%). No systemic associations were found. The lesions all appeared as an elevated subretinal mass, with OCT demonstrating all lesions to be confined to the sclera, not the choroid. On OCT, the deep lesion margin was visible in 12 eyes with a mean lesion thickness of 0.6 mm. Overlying choroidal thinning or absence was seen in 95% (mean choroidal thickness, 28 ± 35 µm). Mild subretinal fluid was observed overlying the lesions in 9 patients (14%). Retinal pigment epithelial disruption and overlying retinal thinning was observed in 56% and 57%, respectively. OCT angiography was performed in 13 eyes and demonstrated associated choroidal and lesional flow voids. Four lesions (6%) were identified at the macula, leading to visual loss in 1 patient. One lesion demonstrated growth and another lesion showed spontaneous resolution. CONCLUSIONS: In this largest series to date, multimodal imaging of SIC demonstrated a scleral location in all patients. The yellow and white clinical appearance may be related to scleral unmasking resulting from atrophy of overlying tissues. Additional associated features included documentation of deep margin on swept-source OCT, trace subretinal fluid in a few patients, and OCTA evidence of lesional flow voids. Because of the scleral location of this lesion in every patient, a new name, focal scleral nodule, is proposed.

Macular Hole-Related Retinal Detachment in Children with Knobloch Syndrome.

PURPOSE: To describe the findings and the management of macular hole (MH)-related retinal detachment (RD) in children with Knobloch syndrome. DESIGN: Retrospective interventional case series. PARTICIPANTS: Patients with Knobloch syndrome who presented with MH-related RD. METHODS: Retrospective chart review of patients with Knobloch syndrome who presented with MH-related RD from January 2012 to December 2018. Interventions included pars plana vitrectomy and silicone oil tamponade with or without scleral buckle, drainage retinotomy, or relaxing retinectomy. MAIN OUTCOME MEASURES: MH characteristics and surgical anatomical outcome. RESULTS: The study included 9 eyes of 5 patients (age range 2 months to 5 years; median age 5.5 months). Presenting symptoms were poor fixation and nystagmus. The fellow eye of 1 patient had RD due to peripheral breaks. The MH was clinically visible in 8 eyes and detected only by OCT in 1 eye. The RD was shallow and extended to the anterior equator in 7 eyes and localized to a punched-out atrophic lesion in 1 eye. Seven eyes underwent surgical repair. At the last follow-up examination (follow-up range 11 to 42 months; mean 24 months, standard deviation 11.8 months), retinal reattachment with MH closure was achieved in 5 eyes along with marked improvement in fixation. CONCLUSION: Patients with Knobloch syndrome may develop MH-related RD as early as infancy. The condition may be easily overlooked in children but should be suspected in the setting of high myopia, vitreoretinal degeneration, and encephalocele.

Delayed spontaneous closure of blue laser-induced full thickness macular hole.

PURPOSE: To report a blue laser-induced full thickness macular hole (FTMH) with delayed spontaneous closure without surgical intervention. OBSERVATIONS: A 14-year old male developed full thickness macular hole after momentary exposure to a high-power handheld blue laser device. The macular hole closed spontaneously over a long period of observation. CONCLUSION: Despite an initial enlargement in size, small FTMH caused by blue lasers may close spontaneously over an extended period of observation.

Familial non-syndromic macular pseudocoloboma secondary to homozygous CLDN19 mutation.

PURPOSE: The purpose of this study is to uncover the genetic cause for non-syndromic macular "coloboma" (pseudocoloboma) in three brothers from a consanguineous family. METHODS: Homozygosity mapping for the three affected brothers and whole-exome sequencing in one affected brother, followed by confirmatory Sanger sequencing and segregation analysis of the candidate gene for all immediate family members; molecular modeling of the candidate mutation; and review of clinical, imaging, and laboratory findings. RESULTS: Three otherwise-healthy brothers (age 10, 10, and 6 years) had macular pseudocoloboma. Both parents and the fourth brother were not affected. Parents were first cousins. A novel homozygous missense variant in claudin 19 (CLND19: NM_148960.2:c. 263T>A; p.Val88Glu) segregated with the phenotype, and molecular modeling predicts an unfavorable effect to protein function. All prior reported biallelic CLND19 mutations cause symptomatic hypomagnesemia with hypercalciuria and nephrocalcinosis, often with concurrent macular pseudocoloboma. However, general physical assessment, metabolic profile, and renal imaging for the three affected brothers were normal. CONCLUSIONS: A homozygous CLDN19 mutation can cause macular pseudocoloboma without evidence for systemic disease in children. This is the first reported family with CLDN19 mutations to have an ocular phenotype only; however, those identified to harbor biallelic CLDN19 mutations should be considered at risk for the extraocular manifestations that have previously been associated with mutations in the gene.

The distinct optic disk and peripapillary appearance in Donnai-Barrow syndrome.

INTRODUCTION: Biallelic mutations in low-density lipoprotein-related protein 2 (LRP2) cause the multi-system Donnai-Barrow syndrome (facio-oculo-acoustico-renal syndrome). Although Donnai-Barrow syndrome is recognized as a form of vitreo-retinopathy, the ocular phenotype has not been well defined. The purpose of this study is to document the disk and peripapillary appearance in Donnai-Barrow syndrome. METHODS: Retrospective cases series (five children with low vision from a consanguineous Emirati family known to harbor LRP2 mutation (NM_004525.2: c.7564T>C; p.Y42522H)). RESULTS: All five children had high myopia (spherical equivalent from -15 to -22). One had an ophthalmic phenotypic pathognomonic for Knobloch syndrome, and genetic testing confirmed a homozygous novel COL18A1 mutation (NM_130455.3: c.2978_2987del; p.Pro993Leufs*35) with heterozygosity for the LRP2 mutation. The other four children, confirmed to be homozygous for the LRP2 mutation, had hypertelorism and down-slanting palpebral fissures. Three had spontaneous retinal detachment (two bilateral and one unilateral) with complicated post-surgical courses following retinal detachment repair. The three eyes (two children) without retinal detachment had a consistent unique optic nerve head appearance, with thin emanating vessels and multiple rings of depigmentation that made it difficult to discern the edge of the apparently small and recessed neuroretinal rim. This distinct appearance was also present in the post-surgical eyes which were not phthisical and seemed present in the single published posterior pole image found during literature review. CONCLUSIONS: A distinctive optic nerve head dysgenesis is part of Donnai-Barrow syndrome and can help distinguish its ocular phenotype from other vitreo-retinopathies associated with high myopia.

Anterior Segment Injury by a High-Power Handheld Blue Laser Device.

PURPOSE: To report a case of severe anterior segment inflammation secondary to exposure to a high-power blue laser device. METHODS: Case report. RESULTS: A 14-year-old male presented with redness, pain and decreased vision in his left eye after exposure to blue laser. Examination indicated severe conjunctival injection associated with 4+ cells in the anterior chamber with fibrinous reaction. The posterior pole was normal. CONCLUSION: Blue laser devices are easily available through the Internet. These devices can cause devastating ocular injuries. National safety guidelines are required to regulate use.

Fundus autofluorescence imaging in hereditary retinal diseases.

Fundus autofluorescence (FAF) is a non-invasive retinal imaging modality used in clinical practice to non-invasively map changes at the level of the retinal pigment epithelium (RPE)/photoreceptor complex and alterations of macular pigment distribution. This imaging method is based on the visualization of intrinsic fluorophores and may be easily and rapidly used in routine patient care. Excessive accumulation of lipofuscin granules in the lysosomal compartment of RPE cells represents a common downstream pathogenic pathway in various hereditary and complex retinal diseases. The clinical applications of FAF continue to expand. It is now an essential tool for evaluating macular dystrophies and various hereditary retinal disorders. Fundus autofluorescence (FAF) may detect abnormalities beyond those detected on funduscopic examination, fluorescein angiography (FA) or optical coherence tomography (OCT). Fundus autofluorescence (FAF) imaging is particularly helpful for differential diagnosis, detection and extent delineation of involved retinal areas, genotype-phenotype correlations and monitoring of changes overtime. Given its ease of use, non-invasive nature and value in characterizing retinal disease, FAF enjoys increasing clinical relevance. This review summarizes basic principles and FAF findings in various hereditary retinal diseases.

Biometry, optical coherence tomography, and further clinical observations in Knobloch syndrome.

PURPOSE: Knobloch syndrome is a pathognomonic vitreo-retinopathy that includes zonular weakness, high myopia, and a distinct fundus appearance with tessellation out of proportion to the degree of myopia. Whether myopia in Knobloch syndrome is axial or lenticular is unclear. Also not known are the optical coherence tomography (OCT) correlates to the distinct fundus appearance. In this study we assess cycloplegic refraction, biometry, and macular spectral domain (SD) OCT in children with Knobloch syndrome. METHODS: A retrospective case series of seven children (12 eyes) with Knobloch syndrome. RESULTS: Twelve eyes with attached retinas (seven patients, aged 6-17 years old, mean 11 years) were identified, seven of which had OCT. Best-corrected vision was typically 20/300 or worse. Axial length divided by corneal radius was >3 for all eyes (3.23-3.77, mean 3.52), consistent with axial myopia, and axial lengths (26.58-30.27 mm, mean 28.16) were consistent with spherical equivalent degree of myopia (-10.00 to -18.50, mean -12) when compared to historical controls. OCT revealed lack of choriocapillaries, outer retinal disorganization, and lack of or only rudimentary foveal pit. CONCLUSIONS: Refractions and biometry in Knobloch syndrome are consistent with the myopia being axial. In addition to vitreo-retinopathy, choroidopathy is part of the phenotype and is an anatomical correlate to the distinctive fundus appearance.

The outcomes and prognostic factors of vitrectomy in chronic diabetic traction macular detachment.

PURPOSE: To investigate the outcomes of pars plana vitrectomy (PPV) for chronic diabetic traction macular detachment (CTMD). METHODS: Ninety-six eyes that underwent PPV for CTMD of at least 6 months duration were retrospectively analyzed. Retinal reattachment rate, final vision, and prognostic factors for poor visual outcome were the main outcome measures. RESULTS: All eyes had long-standing TMD (median 12, range: 6-70 months). The median postoperative follow-up was 15 (range: 3-65) months. Eighty-seven eyes (90.6%) had their retina and macula reattached after one PPV. At final examination, 84 eyes (87.5%) had stable vision or at least one line improvement, and three had no light perception. Seventeen (17.7%) and 41 (43%) eyes had preoperative visual acuity of ≥20/200 and ≥5/200 as compared to 40 (41.6%; P=0.0005) and 64 (66.7%; P=0.0014) eyes at final follow-up, respectively. Age >50 years (Odds ratio [OR] =5.84, 95% confidence interval [CI] =1.53-22.19, P=0.01), preoperative vision <20/400 (OR =7.012, 95% CI =1.82-26.93, P=0.005), and ischemic macula (OR =14.13, 95% CI =3.61-55.33, P<0.001) were significantly associated with final vision <20/400. CONCLUSION: PPV for CTMD may be beneficial particularly in patients who are relatively younger and have good baseline vision and no macular ischemia.

Treatment of retinitis pigmentosa due to MERTK mutations by ocular subretinal injection of adeno-associated virus gene vector: results of a phase I trial.

MERTK is an essential component of the signaling network that controls phagocytosis in retinal pigment epithelium (RPE), the loss of which results in photoreceptor degeneration. Previous proof-of-concept studies have demonstrated the efficacy of gene therapy using human MERTK (hMERTK) packaged into adeno-associated virus (AAV2) in treating RCS rats and mice with MERTK deficiency. The purpose of this study was to assess the safety of gene transfer via subretinal administration of rAAV2-VMD2-hMERTK in subjects with MERTK-associated retinitis pigmentosa (RP). After a preclinical phase confirming the safety of the study vector in monkeys, six patients (aged 14 to 54, mean 33.3 years) with MERTK-related RP and baseline visual acuity (VA) ranging from 20/50 to <20/6400 were entered in a phase I open-label, dose-escalation trial. One eye of each patient (the worse-seeing eye in five subjects) received a submacular injection of the viral vector, first at a dose of 150 µl (5.96 × 10(10)vg; 2 patients) and then 450 µl (17.88 × 10(10)vg; 4 patients). Patients were followed daily for 10 days at 30, 60, 90, 180, 270, 365, 540, and 730 days post-injection. Collected data included (1) full ophthalmologic examination including best-corrected VA, intraocular pressure, color fundus photographs, macular spectral domain optical coherence tomography and full-field stimulus threshold test (FST) in both the study and fellow eyes; (2) systemic safety data including CBC, liver and kidney function tests, coagulation profiles, urine analysis, AAV antibody titers, peripheral blood PCR and ASR measurement; and (3) listing of ophthalmological or systemic adverse effects. All patients completed the 2-year follow-up. Subretinal injection of rAAV2-VMD2-hMERTK was associated with acceptable ocular and systemic safety profiles based on 2-year follow-up. None of the patients developed complications that could be attributed to the gene vector with certainty. Postoperatively, one patient developed filamentary keratitis, and two patients developed progressive cataract. Of these two patients, one also developed transient subfoveal fluid after the injection as well as monocular oscillopsia. Two patients developed a rise in AAV antibodies, but neither patient was positive for rAAV vector genomes via PCR. Three patients also displayed measurable improved visual acuity in the treated eye following surgery, although the improvement was lost by 2 years in two of these patients. Gene therapy for MERTK-related RP using careful subretinal injection of rAAV2-VMD2-hMERTK is not associated with major side effects and may result in clinical improvement in a subset of patients.

Rhegmatogenous retinal detachments associated to Stickler syndrome in a tertiary eye care center in Saudi Arabia.

PURPOSE: To investigate the clinical findings and outcomes of rhegmatogenous retinal detachment (RRD) in Stickler syndrome on affected and fellow eyes that underwent prophylactic retinopexy. PATIENTS AND METHODS: Chart review of 70 eyes (62 patients). Incidence of RRD, postoperative visual acuity, and risk factors were evaluated. RESULTS: Twenty-two patients (35%) had RRD in the fellow eye, 37% of the eyes had cataract, 93% had macular detachment, 50% had proliferative vitreoretinopathy, and 41% had posterior vitreous detachment. Success rates were: 60% of patients after scleral buckling; 57.1% after pars plana vitrectomy; and 75% after combined scleral buckling and pars plana vitrectomy. Sixty-one (93.8%) of patients had successful surgery (including second surgery). Silicone oil tamponade was significantly associated with final anatomic outcome, with a protective odds ratio of 0.11 (P=0.027). Visual acuity improved in 54% of eyes and decreased in 5%. Statistically significant associations were present for eyes with final visual acuity ≥20/200, and total retinal detachment (P<0.001); preoperative cataract (P=0.023); and proliferative vitreoretinopathy (P<0.001). RRD developed in 16/44 eyes despite laser prophylaxis. CONCLUSION: Prophylactic retinopexy was not beneficial for Stickler syndrome patients. Success of primary surgery for RRD remains low. The primary surgery should be vitrectomy combined with scleral buckling and silicone oil tamponade.