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To report the concurrent presentation and management of IQCB1-associated Leber Congenital Amaurosis and NDP-associated Familial Exudative Vitreoretinopathy (FEVR). A 6-month-old Caucasian infant presented with poor visual response, high hypermetropia, and infantile-nystagmus with a provisional diagnosis of Leber Congenital Amaurosis based on clinical findings. Genetic counseling and testing were performed with a 285 gene retinal dystrophy panel (Blueprint Genetics). Clinical characteristics, presentation, ancillary testing results, and management are described. Two previously reported heterozygous pathogenic variants in ICQB1 were identified (c.1518_1519del (p.His506Glnfs*13) and c.1381C>T, p.Arg461*) segregating in trans. In addition, a variation of uncertain significance (VUS) was found in NDP (c.280C>T; p.His94Tyr). Fluorescein angiography was performed demonstrating peripheral avascularity and retinal telangiectasia without frank neovascularization. Peripheral ablative laser was applied to the avascular zone. The NDP VUS likely represents a pathogenic variant given the FEVR phenotype in addition to retinal degeneration, creating a rare dual phenotype. The combination of low oxygen demand from the IQCB1-associated retinal degeneration and NDP variant may have led to a more attenuated FEVR presentation with uncertain prognosis. A molecular diagnosis informed ocular and renal surveillance, as well as the recurrence risk for future offspring. [ABSTRACT FROM AUTHOR]

Purpose: To report complications after serial anterior chamber (AC) paracentesis for sustained elevation of intraocular pressure after intravitreal injection. Methods: A retrospective interventional case series of five patients who had received AC paracentesis after intravitreal injection. Results: Five patients presented with either decreased vision or increased pain after intravitreal injection with planned AC paracentesis. Of the five patients, three patients presented with profound hypotony due to persistent wound leak from the AC paracentesis site. Of these three, one resolved with pressure patch and cycloplegia. The other two patients required further intervention with either polyethylene glycol hydrogel or nylon suture for wound closure. The fourth patient presented with IOL optic prolapse into the AC that resolved with dilation. The fifth patient presented with vitreous prolapse through the AC paracentesis wound and was treated with YAG vitreolysis. Conclusion: A single AC paracentesis has been shown to demonstrate a favorable safety profile. Serial AC paracenteses may degrade the integrity of the peripheral cornea in patients with sustained elevation of intraocular pressure after repeated intravitreal injections. [ABSTRACT FROM AUTHOR]

This retrospective, interventional, sequential, noncomparative case series evaluated surgical outcomes of eyes that underwent same-day combined phacoemulsification surgery for cataract with multifocal intraocular lens implantation and pars plana vitrectomy for symptomatic vitreous opacities. Purpose: To report surgical outcomes of combined vitrectomy for vitreous floaters and phacoemulsification surgery with multifocal intraocular lens implantation. Methods: Retrospective, interventional, noncomparative case series of five eyes from five patients who underwent same-day combined phacoemulsification surgeries with apodized, diffractive multifocal intraocular lens implantation for cataract and pars plana vitrectomy for symptomatic vitreous opacities, that is, floaters. Primary outcomes were distance and near visual acuities, and resolution of symptoms. Secondary outcomes included intraocular pressure, refractive outcomes, and surgical complications. Results: Mean logarithm of the minimum angle of resolution glare distance visual acuity improved from 0.36 (best-corrected Snellen 20/47) preoperatively to an uncorrected distance visual acuity of 0.05 (Snellen 20/23) at 6 months postoperatively (P = 0.042). All but one patient achieved multifocality with a near visual acuity of J2 or better. All patients noted subjective improvement in symptoms from floaters postoperatively. Mean intraocular pressure remained stable during follow-up. Two eyes ultimately required YAG capsulotomies for symptomatic posterior capsular opacification, one of which additionally received LASEK for refractive correction. Conclusion: Multifocality and improvement in symptoms from symptomatic vitreous opacities were observed in this pilot series of carefully selected patients who underwent combined phacovitrectomy with multifocal intraocular lens implantation. A high rate of retinal tears was found in these patients. Appropriate caution should be taken in preoperative assessment and patient selection for the combined procedure. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate if off-label Age-Related Eye Disease Study 2 (AREDS2) supplementation prevents visual and anatomical deterioration in non-proliferative Idiopathic Macular Telangiectasia Type 2 (IMT2). Patients and Methods: This is a single-center retrospective, comparative study of 82 IMT2 eyes treated with AREDS2 from January 1st, 2013 to January 1st, 2018. The study analysis consisted of a non-comparative arm, which included all AREDS2 eyes, and a comparative arm (27 AREDS2 and 42 untreated eyes) that only included eyes with complete follow-up data. Eyes were evaluated at baseline, 12 and 24 months. Better/worse eye sub-analysis was performed in the comparative study arm. Primary outcomes were best corrected visual acuity (BCVA) and optical coherence tomography (OCT) anatomical characteristics including largest cavitation diameter, central macular thickness (CMT), and length of ellipsoid zone (EZ) loss at 24 months. Results: In the non-comparative arm, AREDS2 eyes showed stable BCVA (0.28 ± 0.18 logMAR at baseline vs 0.26 ± 0.19 logMAR at 24 months; p = 0.35) and OCT anatomical features after 24 months of supplementation. In the comparative arm, BCVA mean difference was greater for untreated eyes at 24 months (− 0.09 ± 0.15 vs 0.03 ± 0.11 logMAR; p = < 0.001). AREDS2 eyes had decreased cavitary diameter and EZ loss compared to untreated eyes at the study endpoint (p = 0.01 and p = 0.02, respectively). CMT remained stable for both cohorts throughout the study. For better/worse eye analysis, untreated eyes had worse BCVA at 24 months in both better and worse eyes (both p = 0.01). For anatomical outcomes, increases in both EZ loss (p = 0.04) and cavitary diameter (p = 0.001) among untreated eyes were only significant for eyes with worse baseline BCVA. Conclusion: Our results suggest that off-label AREDS2 supplementation in non-proliferative IMT2 may prevent anatomical and visual deterioration in a subset of eyes. [ABSTRACT FROM AUTHOR]

Nanophthalmos is a rare, potentially devastating eye condition characterized by small eyes with relatively normal anatomy, a high hyperopic refractive error, and frequent association with angle closure glaucoma and vision loss. The condition constitutes the extreme of hyperopia or farsightedness, a common refractive error that is associated with strabismus and amblyopia in children. NNO1 was the first mapped nanophthalmos locus. We used combined pooled exome sequencing and strong linkage data in the large family used to map this locus to identify a canonical splice site alteration upstream of the last exon of the gene encoding myelin regulatory factor (MYRF c.3376-1G>A), a membrane bound transcription factor that undergoes autoproteolytic cleavage for nuclear localization. This variant produced a stable RNA transcript, leading to a frameshift mutation p.Gly1126Valfs*31 in the C-terminus of the protein. In addition, we identified an early truncating MYRF frameshift mutation, c.769dupC (p.S264QfsX74), in a patient with extreme axial hyperopia and syndromic features. Myrf conditional knockout mice (CKO) developed depigmentation of the retinal pigment epithelium (RPE) and retinal degeneration supporting a role of this gene in retinal and RPE development. Furthermore, we demonstrated the reduced expression of Tmem98, another known nanophthalmos gene, in Myrf CKO mice, and the physical interaction of MYRF with TMEM98. Our study establishes MYRF as a nanophthalmos gene and uncovers a new pathway for eye growth and development. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the functional and anatomical outcomes of combined phacovitrectomy with multifocal intraocular lens (mfIOL) implantation. Methods: Retrospective, interventional, non-comparative case series of six eyes that received a combined phacoemulsification surgery with apodized, diffractive mfIOL implantation for cataract and pars plana vitrectomy (PPV) with membrane peeling for epiretinal membrane (ERM). Outcome measures included distance and near visual acuities (DVA and NVA), central macular thickness (CMT), intraocular pressure (IOP), and disruption of external limiting membrane (ELM) or inner-segment outer-segment (IS/OS) junction. Results: Mean logMAR glare DVA improved from 0.40 (Snellen 20/50) preoperatively to a mean uncorrected DVA of 0.038 (Snellen 20/22) (P=0.004) at 6 months after surgery. All eyes achieved NVA of J2 or better by 12 months postoperatively. Median CMT improved by 10 µm and mean IOP increased by 1 mmHg at 12 months postoperatively. Percentage of patients with ELM or IS/OS disruptions decreased from 66.7% to 33.3%. Two eyes demonstrated residual metamorphopsia on Amsler grid testing postoperatively. Postoperatively, four eyes required laser capsulotomy and one required LASEK for refractive correction. Conclusion: Combined phacovitrectomy, membrane peeling, and mfIOL implantation improved VA in patients with idiopathic ERM. Multifocality was achieved, but final visual outcome was delayed due to posterior capsular opacification and macular healing. [ABSTRACT FROM AUTHOR]

Purpose. To present new clinical features, multimodal and ultrawide-field imaging characteristics of peripheral cone dystrophy (PCD), and results of laboratory and genetic investigation to decipher the etiology. Methods. Retrospective observational case-series. Results. Three patients with PCD presented with bilateral paracentral scotomas and a mean visual acuity of 20/25. All exhibited confluent macular hyperautofluorescence with a central bull’s eye lesion. Spectral-domain optical coherence tomography revealed loss of outer retinal elements, particularly the inner segment ellipsoid band and external limiting membrane, within the area of macular hyperautofluorescence. This area corresponded with a lightened fundus appearance and variable retinal pigment epithelium (RPE) abnormalities. Full field and multifocal electroretinography distinguished PCD from other photoreceptor dystrophies. Ultrawide-field imaging revealed irregular peripheral retinal lesions in a distribution greater nasally than temporally and not contiguous with the macular lesion. Functional and anatomic testing remained stable over a mean follow-up of 3 years. Laboratory investigation for causes of uveitis was negative. Whole exome sequencing identified rare variants in genes associated with macular or cone dystrophy or degeneration. Conclusions. In contrast to the original description, the funduscopic and fluorescein angiographic appearance of PCD is abnormal, although the defects are subtle. Peripheral lesions may be observed in some patients. Bilateral, symmetric, macular hyperautofluorescence associated with outer retinal atrophy that spares the fovea is a characteristic of PCD. Pathogenic variants in the same gene were not shared across the cohort, suggesting genetic heterogeneity. Further evaluation is warranted. [ABSTRACT FROM AUTHOR]

Background Usher syndrome (USH) is a neurosensory disorder characterised by deafness, variable vestibular areflexia and vision loss. The aim of the study was to identify the genetic defect in a Pakistani family (PKDF1051) segregating USH. Methods G enome-wide linkage analysis was performed by using an Illumina linkage array followed by Sanger and exome sequencing. Heterologous cells and mouse organ of Corti explant-based transfection assays were used for functional evaluations. Detailed clinical evaluations were performed to characterise the USH phenotype. Results T hrough homozygosity mapping, we genetically linked the USH phenotype segregating in family PKDF1051 to markers on chromosome 1p36.32-p36.22. The locus was designated USH1M. Using a combination of Sanger sequencing and exome sequencing, we identified a novel homozygous 18 base pair inframe deletion in ESPN. Variants of ESPN, encoding the actinbundling protein espin, have been previously associated with deafness and vestibular areflexia in humans with no apparent visual deficits. Our functional studies in heterologous cells and in mouse organ of Corti explant cultures revealed that the six deleted residues in affected individuals of family PKDF1051 are essential for the actin bundling function of espin demonstrated by ultracentrifugation actin binding and bundling assays. Funduscopic examination of the affected individuals of family PKDF1051 revealed irregular retinal contour, temporal flecks and disc pallor in both eyes. ERG revealed diminished rod photoreceptor function among affected individuals. Conclusion Our study uncovers an additional USH gene, assigns the USH1 phenotype to a variant of ESPN and provides a 12th molecular component to the USH proteome. [ABSTRACT FROM AUTHOR]

Purpose: To review antibiotic resistance associated with S. aureus endophthalmitis and the virulence of S. aureus.Methods: Review of the current and prospective approaches for treating S. aureus endophthalmitis.Results: Bacterial endophthalmitis remains to be a major threat for vision. S. aureus endophthalmitis specifically, carries a poor visual prognosis making early diagnosis and treatment crucial. Methicillin resistant Staphylococcus aureus (MRSA) endophthalmitis represents a significant number of S. aureus endophthalmitis cases. MRSA with reduced susceptibility to glycopeptide antibiotics such as vancomycin (vancomycin intermediate S. aureus, VISA) have also emerged in the ocular infections, and there has been a rise in S. aureus resistance to new and old generation fluoroquinolones that are commonly used for prophylaxis after intravitreal injections and intraocular surgeries.Conclusions: With the rise in the number of penetrating procedures in the ophthalmology practice and the parallel rise in antibiotic resistance, prophylaxis and awareness of the antimicrobial resistance profiles remain crucial and the identification of novel antimicrobials is essential. [ABSTRACT FROM AUTHOR]

Objective: To assess the combination of scleral buckling (SB) and pars plana vitrectomy (PPV) versus PPV alone in the primary repair of rhegmatogenous retinal detachments (RRDs). Methods: The current study was a retrospective, comparative, interventional, consecutive case series of 179 eyes of 174 patients who underwent primary RRD repair by five surgeons between January 1, 2008 and December 31, 2010, utilizing SB with PPV or PPV. Univariate and multivariate analyses were used to compare the efficacy of the two surgical strategies and assess for risk factors of proliferative vitreoretinopathy (PVR). Results: Single surgery anatomic success (SSAS) was similar (P=0.76) between the PPV group (112 of 132 eyes, 85%) and SB with PPV group (39 of 47 eyes, 83%). Final anatomic success was 100% in each group. There was no difference in rates of PVR formation (PPV 16% vs SB with PPV 19%, P=0.70). Final logarithm of the minimum angle of resolution acuity was 0.33 (20/43) in the PPV group and 0.37 (20/47) in the SB with PPV group (P=0.62). Postoperative anterior chamber fibrin was highly correlated with PVR formation (PVR 13% vs no PVR 0.7%, P=0.003; odds ratio =68.37, P=0.007). Separate analysis of medium- to high-complexity cases showed similar SSAS (PPV 86% vs SB with PPV 83%, P=0.45). Conclusion: SB with PPV versus PPV alone were similarly efficacious for repair of primary RRDs of varying complexity. SSAS rates, PVR incidence, and final visual acuities were not significantly different. [ABSTRACT FROM AUTHOR]

Purpose: To report a case of inadvertent subretinal cannulation of ab externo suture trabeculotomy surgery associated with serous macular detachment. Methods: Retrospective case report. Ophthalmic examination and portable spectral domain optical coherence tomography (Envisu C2300; Bioptogen, Morrisville, NC) were performed under general anesthesia. Results: A 5-year-old girl with uveitis secondary to oligoarticular juvenile idiopathic arthritis underwent trabeculotomy surgery of the left eye for steroid-induced glaucoma refractory to medical management. The surgery was complicated by inadvertent subretinal cannulation with the prolene suture. Multiple, arcuate, hypopigmented subretinal tracks, originating from the ora serrata, were observed. Spectral domain optical coherence tomography images through the macula revealed subretinal fluid overlying funduscopically visible tracks, defects in photoreceptor outer segments overlying the tracks, and normal choroidal anatomy. The serous macular detachment resolved spontaneously after 4 months and visual acuity returned to baseline 20/25 in the left eye, consistent with reversible localized damage to the outer retina and retinal pigment epithelium. Conclusion: We report a case of inadvertent subretinal cannulation during suture trabeculotomy surgery that resulted in serous macular detachment which resolved spontaneously. The inadvertent complication demonstrated a pathway for administration of therapeutics to the subretinal space. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate intravitreal methotrexate infusion (IMI) during pars plana vitrectomy (PPV) for retinal detachment in patients with high risk for the development of proliferative vitreoretinopathy (PVR). Methods: Patients presenting with severe recurrent PVR with tractional retinal detachment and/or a history of severe ocular inflammation were treated with IMI. Clinical outcomes were determined from a retrospective medical chart review. Results: Twenty-nine eyes presenting with either tractional retinal detachment and recurrent PVR (n=22) or a history of severe inflammation associated with high PVR risk (n=7) received IMI during PPV. Best-corrected visual acuity at 6 months was ≥20/200 in 19 of 29 eyes (66%) and remained stable or improved compared with initial presentation in 24 of 29 eyes (83%). At the last follow-up examination, the retinas of 26 of 29 eyes (90%) remained attached after IMI while three eyes required another reattachment procedure. Three additional eyes (10%) developed recurrent limited PVR without recurrent RD and were observed. No complications attributable to IMI occurred during a mean follow-up of 27 months. Conclusion: Eyes at high risk for PVR development due to a history of prior PVR or intraocular inflammation had a low incidence of PVR following IMI at the time of PPV for RD repair. No significant safety issues from IMI were observed in this series. [ABSTRACT FROM AUTHOR]

Aim: Our specific aim was to document the pathoetiologic importance of thrombophilia among females presenting with severe ischemic retinal vein (RVO) or retinal artery (RAO) occlusion, without typical risk factors, and to emphasize that the ophthalmologists' diagnosis of thrombophilia has important diagnostic and therapeutic downstream ramifications for nonocular thrombosis, including reproductive outcomes. Methods: We evaluated familial and acquired thrombophilia in 60 females with RVO (central RVO, n=52; branch RVO, n=8) and 16 with RAO (central RAO, n=11; branch RAO, n=5). They were referred by retinologists, without typical risk factors for RVO/RAO and/or severe ocular ischemic presentation. We focused on extraocular thrombotic events, particularly pregnancy complications, including unexplained spontaneous abortion, pre-eclampsia-eclampsia. Thrombophilia measurements in the 76 females were compared with 62 healthy normal females without ocular vascular occlusions (OVOs). Results: The 76 females with OVO were more likely than 62 normal female controls to have high homocysteine (24% vs 0%, P<0.0001), high anticardiolipin antibody (immunoglobulin M, 17% vs 3%, P=0.012), high (>150%) factor VIII (42% vs 11%, P<0.0001), and high (>150%) factor XI (22% vs 4%, P=0.004). Of the 76 females, 26 (34%) had ⩾1 spontaneous abortion; 17 (22%) had ⩾2 spontaneous abortions and/or pre-eclampsia-eclampsia. Compared to 62 healthy female controls, these 17 females with pregnancy complications had high homocysteine (29% vs 0%, P=0.0003), high anticardiolipin antibody immunoglobulin M (24% vs 3%, P=0.02), high factor VIII (38% vs 11%, P=0.02), and were marginally more likely to be heterozygous for the factor V Leiden mutation (19% vs 3%, P=0.058). Conclusion: In females lacking typical risk factors for retinal vascular occlusion or severely ischemic presentation, by diagnosing thrombophilia as an etiology for OVO, the ophthalmologist opens a window to family screening and preventive therapy, with particular relevance to pregnancy outcomes and venous thromboembolism. [ABSTRACT FROM AUTHOR]

Background: X-linked retinoschisis is one of the more frequently encountered inherited macular retinal disorders affecting young males, causing loss of vision. Patients exhibit macular schisis and peripheral schisis, which can mimic retinal detachment, a very different entity that requires surgical intervention. Case Presentation: An 8-month-old African-American boy was presented to our hospital with severe X-linked retinoschisis involving symmetrical bullous peripheral retinoschisis in both eyes, mimicking retinal detachment. One eye received multiple surgeries for retinal detachment repair that were complicated by proliferative vitreoretinopathy. Later, portable optical coherence tomography was used to confirm absence of retinal detachment despite a corrugated fundus appearance in the fellow eye. Following treatment with topical dorzolamide 2 % for 18 months, there was dramatic regression of both macular and peripheral schisis cavities in the nonoperative eye. Conclusions: Severe bullous peripheral schisis in infants with severe X-linked retinoschisis may produce posterior corrugations that mimic rhegmatogenous retinal detachment. Clinical suspicion for retinal detachment in infants with X-linked retinoschisis should be confirmed by portable optical coherence tomography before surgical intervention. Bullous peripheral schisis can remain clinically stable over time, but topical dorzolamide 2 % may facilitate collapse. [ABSTRACT FROM AUTHOR]

Background: Ocular vascular occlusion (OVO), first diagnosed during or immediately after giving birth, often reflects superposition of the physiologic thrombophilia of pregnancy on previously undiagnosed underlying familial or acquired thrombophilia associated with spontaneous abortion, eclampsia, or maternal thrombosis. Specific aim: We describe OVO, first diagnosed during pregnancy or immediately postpartum, in three young females (ages 32, 35, 40) associated with previously undiagnosed familial thrombophilia. Results: Branch retinal artery occlusion (BRAO) occurred at 9 and 13 weeks gestation in two females, aged 32 and 35. Central retinal vein occlusion occurred immediately postpartum in a 40-year-old. One of the two females with BRAO subsequently developed eclampsia, and one had a history of unexplained first trimester spontaneous abortion. All three females were found to have previously unexplained familial thrombophilia. The two females with BRAO had low first trimester free protein S 42 (41%), lower normal limit (50%), and one of these two had high factor VIII (165%, upper normal limit 150%). The woman with central retinal vein occlusion had high factor XI (169%, upper normal limit 150%). Enoxaparin (40-60 mg/day) was started and continued throughout pregnancy in both females with BRAO to prevent maternal-placental thrombosis, and of these two females, one had an uncomplicated pregnancy course and term delivery, and the second was at gestational week 22 without complications at the time of this manuscript. There were no further OVO events in the two females treated with enoxaparin or in the untreated patient with postpartum eclampsia. Conclusion: OVO during pregnancy may be a marker for familial or acquired thrombophilia, which confers increased thrombotic risk to the mother and pregnancy, associated with spontaneous abortion or eclampsia. OVO during pregnancy, particularly when coupled with antecedent adverse pregnancy outcomes, should prompt urgent thrombophilia evaluation and institution of thromboprophylaxis to prevent adverse maternal and fetal-placental thrombotic events. [ABSTRACT FROM AUTHOR]

We report three cases of idiopathic macular telangiectasia type 2 with temporally decentered preretinal hemorrhage as the presenting sign. The preretinal blood obscured the telangiectatic vessels such that the diagnosis was only evident by fluorescein angiography of the fellow eyes, which had near-normal vision. The preretinal hemorrhage was associated with Valsalva maneuver in one patient and with type 3 subretinal neovascularization in one patient. We speculate that the vascular dilations in idiopathic macular telangiectasia type 2 may increase patients' susceptibility to rupture and hemorrhage with increased venous pressure. [ABSTRACT FROM AUTHOR]