Familial Exudative Vitreoretinopathy With and Without Pathogenic Variants of Norrin/ß-Catenin Signaling Genes.

Purpose: To determine the clinical characteristics of familial exudative vitreoretinopathy (FEVR) associated with or without pathogenic variants of the Norrin/ß-catenin genes. Design: This was a multicenter, cross-sectional, observational, and genetic study. Subjects: Two-hundred eighty-one probands with FEVR were studied. Methods: Whole-exome sequence and/or Sanger sequence was performed for the Norrin/ß-catenin genes, the FZD4, LRP5, TSPAN12, and NDP genes on blood collected from the probands. The clinical symptoms of the probands with or without the pathogenic variants were assessed as well as differences in the inter Norrin/ß-catenin genes. Main Outcome Measures: The phenotype associated with or without pathogenic variants of the Norrin/ß-catenin genes. Results: One-hundred eight probands (38.4%) had 88 different pathogenic or likely pathogenic variants in the genes: 24 with the FZD4, 42 with the LRP5, 10 with the TSPAN12, and 12 with the NDP gene. Compared with the 173 probands without pathogenic variants, the 108 variant-positive probands had characteristics of familial predisposition (63.9% vs. 37.6%, P < 0.0001), progression during infancy (75.0% vs. 53.8%, P = 0.0004), asymmetrical severity between the 2 eyes (50.0% vs. 37.6%, P = 0.0472), and nonsyndromic characteristics (10.2% vs. 17.3%, P = 0.1185). The most frequent stage at which the more severe eye conditions was present was at stage 4 in both groups (40.7% vs. 34.7%). However, the advanced stages of 3 to 5 in the more severe eye were found more frequently in probands with variants than in those without variants (83.3% vs. 58.4%, P < 0.0001). Patients with rhegmatogenous retinal detachments progressed from stage 1 or 2 were found less frequently in the variant-positive probands (8.3% vs. 17.3%, P = 0.0346). Nine probands with NDP variants had features different from probands with typical Norrin/ß-catenin gene variants including the sporadic, symmetrical, and systemic characteristics consistent with Norrie disease. Conclusions: The results showed that the clinical characteristics of FEVR of patients with variants in the Norrin/ß-catenin genes are different from those with other etiologies. We recommend that clinicians who diagnose a child with FEVR perform genetic testing so that the parents can be informed on the prognosis of the vision and general health in the child. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Measurement of paracentral stereopsis using a new method with the binocular open perimeter imovifa® in normal adults.

PURPOSE: No method to quantitatively evaluate stereopsis within the 15º visual field has been clinically established. We developed a program to measure paracentral stereopsis and evaluated its feasibility in visually normal participants. STUDY DESIGN: Experimental investigation METHODS: Ten visually normal volunteers with stereopsis of 60 arcseconds or better were included. The Stereo Eccentricity Analysis (SEA) program for stereopsis measurement across the visual field was integrated into the binocular visual field analyzer imovifa®. Subjects with established binocular stereopsis detected a stereoscopic circular target presented with crossed disparity on random dots at the fovea, 3°, 5°, 10°, and 15° on the 45°, 135°, 225°, and 315° meridians. The subjects performed two tasks for measurement in the periphery: a detection task by pressing the response button when the circular target was perceived and a localization task by tilting a joystick to indicate in which quadrant the circular target was perceived. The duration of the target presentation was 500 ms. RESULTS: The stereo thresholds at 0º and 3° did not significantly differ. The thresholds at 10º and 15º were significantly higher than at 0° (P < 0.01). While no inter-individual threshold difference was observed at the fovea, the difference was large at 15°. The stereo thresholds for the detection and localization tasks also did not differ significantly. CONCLUSION: With the SEA program, paracentral stereopsis can be measured and the stereo threshold increases with eccentricity. The SEA program appears to be a feasible clinical method to evaluate paracentral stereopsis.

Clinical course of two siblings with potassium voltage-gated channel modifier subfamily V member 2 (KCNV2)-associated retinopathy.

BACKGROUND: KCNV2-associated retinopathy causes a phenotype reported as "cone dystrophy with nyctalopia and supernormal rod responses (CDSRR; OMIM# 610356)," featuring pathognomonic findings on electroretinography (ERG). Here, we report the clinical courses of two siblings with CDSRR. CASE REPORTS: Patient 1: A 3-year-old boy with intermittent exophoria was referred to our hospital. The patient's decimal best-corrected visual acuity (BCVA) at age 6 was 0.7 and 0.7 in the right and left eyes, respectively. Photophobia and night blindness were also observed. Because the ERG showed a delayed and supernormal b-wave with a "squaring (trough-flattened)" a-wave in the DA-30 ERG, and CDSRR was diagnosed. The patient's vision gradually worsened, and faint bilateral bull's eye maculopathy was observed at the age of 27 years, although the fundi were initially unremarkable. Genetic examination revealed a homozygous missense variant, c.529T > C (p.Cys177Arg), in the KCNV2 gene. Patient 2: The second patient was Patient 1's younger sister, who was brought to our hospital at 3 years of age. The patient presented with exotropia, mild nystagmus, photophobia, night blindness, and color vision abnormalities. The patients' decimal BCVA at age 13 was 0.6 and 0.4 in the right and left eyes, respectively, and BCVA gradually decreased until the age of 24 years. The fundi were unremarkable. The siblings had similar ERG findings and the same homozygous missense variant in the KCNV2 gene. CONCLUSIONS: The siblings had clinical findings typical of CDSRR. High-intense flash ERG is recommended for identifying pathognomonic "squaring" a-waves in patients with CDSRR.

Disease-specific variant interpretation highlighted the genetic findings in 2325 Japanese patients with retinitis pigmentosa and allied diseases.

BACKGROUND: As gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)-related genes in a large number of Japanese patients with RP by applying the standardised variant interpretation guidelines for Japanese patients with IRD (J-IRD-VI guidelines) built upon the American College of Medical Genetics and Genomics and the Association for Molecular Pathology rules, and assess the contribution of these genes in RP-allied diseases. METHODS: We assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, newly analysed), including Usher syndrome, Leber congenital amaurosis and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines. RESULTS: A total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 patients with RP. This led to a genetic diagnostic rate in 38.6% of patients with RP, with EYS accounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for patients with CRD was 28.2%, with RP-related genes significantly contributing over other allied diseases. CONCLUSION: A large-scale genetic analysis using the J-IRD-VI guidelines highlighted the population-specific genetic findings for Japanese patients with IRD; these findings serve as a foundation for the clinical application of gene-specific therapies.

Genetic and Clinical Features of ABCA4-Associated Retinopathy in a Japanese Nationwide Cohort.

PURPOSE: To clarify the genetic and clinical features of Japanese patients with ABCA4-associated retinopathy. DESIGN: Retrospective, multicenter cohort study. METHODS: Patients with retinal degeneration and biallelic ABCA4 variants were recruited from 13 different hospitals. Whole exome sequencing analysis was used for genetic testing. Comprehensive ophthalmic examinations were performed on matched patients. The primary outcome measure was identifying multimodal retinal imaging findings associated with disease progression. RESULTS: This study included 63 patients: 19 with missense/missense, 23 with missense/truncation, and 21 with truncation/truncation genotypes. In total, 62 variants were identified, including 29 novel variants. Six patients had a mild phenotype characterized by foveal-sparing or preserved foveal structure, including 4 with missense/missense and 2 with missense/truncation genotypes. The p.Arg212His variant was the most frequent in patients with mild phenotypes (4/12 alleles). Clinical findings showed a disease duration-dependent worsening of the phenotypic stage. Patients with the truncation/truncation genotype exhibited rapid retinal degeneration within a few years and definite fundus autofluorescence imaging patterns, including hyper autofluorescence at the macula and few or no flecks. CONCLUSIONS: Our results indicate that missense/missense or missense/truncation genotypes, including the p.Arg212His variant, are associated with a relatively mild phenotype. In contrast, the truncation/truncation genotype causes rapid and severe retinal degeneration in Japanese patients with ABCA4-associated retinopathy. These data are vital in predicting patient prognosis, guiding genetic counseling, and stratifying patients for future clinical trials.

Substance P promotes transforming growth factor-ß-induced collagen synthesis in human corneal fibroblasts.

Corneal fibroblasts maintain homeostasis of the corneal stroma by mediating the synthesis and degradation of extracellular collagen, and these actions are promoted by transforming growth factor-ß (TGF-ß) and interleukin-1ß (IL-1ß), respectively. The cornea is densely innervated with sensory nerve fibers that are not only responsible for sensation but also required for physiological processes such as tear secretion and wound healing. Loss or dysfunction of corneal nerves thus impairs corneal epithelial wound healing and can lead to neurotrophic keratopathy. The sensory neurotransmitter substance P (SP) promotes corneal epithelial wound healing by enhancing the stimulatory effects of growth factors and fibronectin. We have now investigated the role of SP in collagen metabolism mediated by human corneal fibroblasts in culture. Although SP alone had no effect on collagen synthesis or degradation by these cells, it promoted the stimulatory effect of TGF-ß on collagen type I synthesis without affecting that of IL-1ß on the expression of matrix metalloproteinase-1. This effect of SP on TGF-ß-induced collagen synthesis was accompanied by activation of p38 mitogen-activated protein kinase (MAPK) signaling and was attenuated by pharmacological inhibition of p38 or of the neurokinin-1 receptor. Our results thus implicate SP as a modulator of TGF-ß-induced collagen type I synthesis by human corneal fibroblasts, and they suggest that loss of this function may contribute to the development of neurotrophic keratopathy.NEW & NOTEWORTHY This study investigates the role of substance P (SP) in collagen metabolism mediated by human corneal fibroblasts in culture. We found that, although SP alone had no effect on collagen synthesis or degradation by corneal fibroblasts, it promoted the stimulatory effect of transforming growth factor-ß on collagen type I synthesis without affecting that of interleukin-1ß on the expression of matrix metalloproteinase-1.

Sweeping technique for the removal of emulsified silicone oil droplets from the anterior surface of the iris using an ophthalmic absorption sponge.

PURPOSE: Silicone oil (SO) tamponade is frequently used in complex vitreoretinal surgeries, and SO migration into the anterior chamber can lead to complications such as glaucoma and corneal decompensation. A new technique is described for the efficient removal of emulsified SO droplets, which can adhere strongly to the anterior surface of the iris. METHODS: The tip of an ophthalmic absorption sponge was cut to an approximately 1x1 mm size. Using forceps, the sponge was inserted through a 25-gauge trocar, then through a corneal paracentesis, to gently scrape the surface of the iris to dislodge the adherent SO droplets, which were subsequently aspirated. RESULTS: This technique efficiently and effectively dislodged and mobilized most emulsified SO droplets, thereby allowing removal via aspiration using a vitrector. Two months after surgery, the retina remained attached, the intraocular pressure decreased from 18 mmHg to 15 mmHg, and there were no visible SO droplets in the anterior chamber. CONCLUSION: The sweeping technique is a safe and efficient method to dislodge, mobilize and aspirate emulsified SO droplets that are adherent to the anterior surface of the iris, thereby decreasing the risk of future SO-related complications.

Optical coherence tomography findings of the peripheral retina in patients with congenital X-linked retinoschisis.

Introduction: Congenital X-linked retinoschisis (XLRS) presents as macular retinoschisis/degeneration in almost all patients and as peripheral retinoschisis in half the patients. Although the optical coherence tomography (OCT) findings of macular retinoschisis have been well investigated, those of peripheral retinoschisis have rarely been reported. This study aimed to report the ultra-widefield OCT findings of the peripheral retina in patients with XLRS. Methods: Medical records of 10 Japanese patients (19 eyes) with clinically and/or genetically diagnosed XLRS were retrospectively reviewed. Funduscopic, electroretinographic, and OCT findings were reviewed and evaluated. Some were also genetically evaluated for the RS1 gene. Results: OCT of the macula revealed schises and/or cystoid changes in the inner nuclear layer (INL) and outer nuclear layer. In contrast, OCT of the peripheral retina revealed schises and/or cystoid changes in the INL in eight eyes (44%), and/or splitting in the ganglion cell layer (GCL) in 10 (56%) of the 18 eyes with clear OCT images. No schisis or cystoid changes were found in the peripheral OCT images of eight eyes (44%). A 16-year-old boy presented with retinal splitting of the GCL and INL of the inferior retina, although he had no ophthalmoscopic peripheral retinoschisis. Genetic examinations were performed on three patients, all of whom had reported missense mutations in the RS1 gene. Conclusion: In XLRS, peripheral bullous retinoschisis results from GCL splitting in the retina. One of the 10 patients with XLRS showed intraretinal retinoschisis in the GCL in the inferior periphery, which was unremarkable on ophthalmoscopy (occult retinoschisis). Although both peripheral bullous retinoschisis and occult retinoschisis showed splitting/cystic changes in the GCL, further studies are needed to determine whether occult retinoschisis progresses to bullous retinoschisis.

Factors affecting the total occlusion time in eyes with hyperopic anisometropic amblyopia.

BACKGROUND: Amblyopia treatment by occluding the healthy eye is known to be effective during a sensitive critical period. This study aims to clarify the factors for the total occlusion time (TOT) required for the amblyopic eye to achieve a normal visual acuity (VA) level of 1.0 (0.0 logMAR equivalent). This could contribute to an efficient treatment plan for eyes with hyperopic anisometropic amblyopia. METHODS: Subjects were 58 patients (26 boys and 32 girls; age range, 3.6-9.2, average, 5.8 ± 1.3 years) with hyperopic anisometropic amblyopia. All the subjects had initially visited and completed occlusion therapy with improved VA of 1.0 or better in the amblyopic eye at Kindai University Hospital between January 2007 and March 2017. Using the subjects' medical records, we retrospectively investigated five factors for the TOT: the age at treatment, the initial VA of the amblyopic eye, refraction of the amblyopic eye, anisometropic disparity, and the presence of microstrabismus. Patient's VA improvement at one month after treatment was also evaluated to confirm the effect of the occlusion therapy. RESULTS: The initial VA of the amblyopic eye ranged from 0.1 to 0.9 (median, 0.4). The TOT ranged from 140 to 1795 (median, 598) hours with an average daily occlusion time of 7 hours. The initial VA of the amblyopic eye and presence of microstrabismus were the significant factors for the TOT (p < 0.01). To achieve VA of 1.0 or better, patients with an initial VA of ≤ 0.3 in the amblyopic eye required a longer TOT. Moreover, patients with concomitant microstrabismus required a 1.7-fold longer TOT compared to those without microstrabismus. CONCLUSION: Longer daily occlusion hours and early start of the treatment will be necessary for patients with poor initial VA or microstrabismus to complete occlusion therapy within the sensitive critical period.

Bruton Tyrosine Kinase Inhibitor in 2 Patients With Vitreoretinal Lymphoma.

This case report describes the use of tirabrutinib to treat 2 individuals with vitreoretinal lymphoma.

Development of a joint set of database parameters for the EU-ROP and Fight Childhood Blindness! ROP Registries.

BACKGROUND/AIMS: The incidence of retinopathy of prematurity (ROP) is increasing and treatment options are expanding, often without accompanying safety data. We aimed to define a minimal, patient-centred data set that is feasible to collect in clinical practice and can be used collaboratively to track and compare outcomes of ROP treatment with a view to improving patient outcomes. METHODS: A multinational group of clinicians and a patient representative with expertise in ROP and registry development collaborated to develop a data set that focused on real-world parameters and outcomes that were patient centred, minimal and feasible to collect in routine clinical practice. RESULTS: For babies receiving ROP treatment, we recommend patient demographics, systemic comorbidities, ROP status, treatment details, ophthalmic and systemic complications of treatment, ophthalmic and neurodevelopmental outcomes at initial treatment, any episodes of retreatment and follow-up examinations in the short and long-term to be collected for use in ROP studies, registries and routine clinical practice. CONCLUSIONS: We recommend these parameters to be used in registries and future studies of ROP treatment, to reduce the variation seen in previous reports and allow meaningful assessments and comparisons. They form the basis of the EU-ROP and the Fight Childhood Blindness! ROP Registries.

A new static visual field test algorithm: the Ambient Interactive ZEST (AIZE).

Visual field (VF) test is one of the most vital tests in the diagnosis of glaucoma and to monitor the disease worsening. In the past couple of decades, the standard automated perimetry (SAP) test takes a major role in VF test for glaucoma patients. The SAP has been demanded to finish a test in short time without sacrificing accuracy. In this study, we developed and evaluated the performance of a new perimetric algorithm (ambient interactive zippy estimation by sequential testing (ZEST): AIZE) by computer simulation. AIZE is a modification of the ZEST procedure that utilizes the spatial information (weighted likelihood: WL) of neighboring test locations, which varies from the distance to the tested location, to estimate a visual threshold. Ten glaucomatous and 10 normal empirical visual field (VF) test results were simulated with five error conditions [(3% false positives (FP), 3% false negatives (FN)), (9% FP, 9% FN), (15% FP, 15% FN), (3% FP, 15% FN), (15% FP, 3% FN)]. The total number of test presentations and the root mean square error (RMSE) of the estimated visual sensitivities were compared among AIZE, the non-weighted test (WL = 0) and the fixed-weighted test (WL = 0.33). In both glaucomatous (G) and normal (N) VFs, the fixed-weighted test had the lowest number of test presentations (median G 256, N 139), followed by the AIZE (G 285, N 174) and the non-weighted test (G 303, N 195). The RMSE of the fixed-weighted test was lower (median 1.7 dB) than that of the AIZE (1.9 dB) and the non-weighted test (1.9 dB) for normal VFs, whereas the AIZE had a lower RMSE (3.2 dB) than the fixed-weighted test (4.5 dB) and the non-weighted test (4.0 dB) for glaucomatous VFs. Simulation results showed that AIZE had fewer test presentations than the non-weighted test strategy without affecting the accuracy for glaucomatous VFs. The AIZE is a useful time saving test algorithm in clinical settings.

Fundus autofluorescence, optical coherence tomography and electroretinography abnormalities in a patient with digoxin retinopathy that resemble those in KCNV2-associated retinopathy.

BACKGROUND: Digoxin related retinal toxicity causes blurred vision, photophobia, central scotoma, color vision abnormality, and electroretinography (ERG) abnormalities. Here, we report a case with transient abnormalities in vison, in which fundus autofluorescence (FAF), optical coherence tomography (OCT), and ERG findings resembled those in KCNV2 (potassium voltage-gated channel modifier subfamily V member 2)-associated retinopathy. CASE REPORT: An 89-year-old woman presented with complaints of acute blurred vision, nyctalopia, photophobia, and color vision abnormality. She received digoxin for tachycardia induced by atrial fibrillation for a month. The fundi showed a faint white ring at the fovea, which showed hyperfluorescence in FAF. OCT showed a thickened EZ in the macula. A dark-adapted (DA)-30 ERG showed a reduced and "squaring (trough-flattened)" a-wave, and a delayed, supernormal b-wave, resulting in a high b/a-wave amplitude ratio. The digoxin dose was reduced following an elevation in serum levels. Five weeks later, her visual acuities improved, and abnormal hyperfluorescence on FAF disappeared. After 6 months, no visual symptoms were reported. The ellipsoid-zone thickening in OCT improved; however, the b/a-wave amplitude ratio on DA-30 ERG remained high. The b-wave in LA-long-flash ERG was initially reduced, which improved after correction of serum level of digoxin. CONCLUSIONS: The patient's clinical findings resembled those of patients with KCNV2-associated retinopathy or temporal hyperkalemia. These disorders appear to have a common pathogenesis, which may be related to abnormal extracellular potassium levels in the retina. The on-bipolar cells seemed to be more affected than the off-bipolar cells in digoxin related retinal toxicity.

Use of a Backflush Needle with a Silicone Tip Cannula to Embed Lamellar Hole-Associated Epiretinal Proliferation.

PURPOSE: For the treatment of lamellar macular hole, the recent development of a lamellar hole-associated epiretinal proliferation (LHEP) embedding technique is likely to improve functional and anatomical results. However, the peeling of LHEP is often technically challenging. We have developed a new technique using a backflush needle with a silicone tip cannula that seems safer and more effective for use in LHEP embedding. METHODS: A 25-gauge vitrectomy system with an enhancing visual acuity system (D.O.R.C., Zuidland, Netherlands) was used in all cases. After core vitrectomy, triamcinolone acetonide (Wakamoto Pharmaceutical Co., Ltd., Tokyo, Japan) was used to visualize the membrane. A 25-gauge backflush needle with a silicone tip cannula was used to remove the thin preretinal membrane centripetally, leaving an LHEP on the edge of the hole. Brilliant Blue G (internal limiting membrane Blue; D.O.R.C.) was then used to stain the internal limiting membrane. RESULTS: This technique was used in six eyes with lamellar macular holes. In all cases, peeling and embedding of the LHEP was effectively performed without damaging the internal limiting membrane or causing retinal hemorrhage. No other intraoperative or postoperative complications were experienced. CONCLUSION: Using a silicone-tipped backflush needle with passive aspiration was a simple and effective technique for peeling and embedding of LHEPs in this small series.

Urokinase-type plasminogen activator promotes corneal epithelial migration and nerve regeneration.

Urokinase-type plasminogen activator (uPA) is a serine protease that plays a central role in the pericellular fibrinolytic system, mediates the degradation of extracellular matrix proteins and activation of growth factors, and contributes to the regulation of various cellular processes including cell migration and adhesion, chemotaxis, and angiogenesis. The corneal epithelium responds rapidly to injury by initiating a wound healing process that involves cell migration, cell proliferation, and tissue remodeling. It is innervated by sensory nerve endings that play an important role in the maintenance of corneal epithelial homeostasis and in the wound healing response. We here investigated the role of uPA in corneal nerve regeneration and epithelial resurfacing after corneal injury with the use of uPA-deficient mice. Both the structure of the corneal epithelium and the pattern of corneal innervation in uPA-/- mice appeared indistinguishable from those in uPA+/+ mice. Whereas the cornea was completely resurfaced by 36-48 h after epithelial scraping in uPA+/+ mice, however, such resurfacing required at least 72 h in uPA-/- mice. Restoration of epithelial stratification was also impaired in the mutant mice. Fibrin zymography revealed that the expression of uPA increased after corneal epithelial scraping and returned to basal levels in association with completion of re-epithelialization in wild-type animals. Staining of corneal whole-mount preparations for ßIII-tubulin also revealed that the regeneration of corneal nerves after injury was markedly delayed in uPA-/- mice compared with uPA+/+ mice. Our results thus demonstrate an important role for uPA in both corneal nerve regeneration and epithelial migration after epithelial debridement, and they may provide a basis for the development of new treatments for neurotrophic keratopathy.

The Association Between Improvement of Stereoacuity and Suppression in the Treatment of Anisometropic Amblyopia.

Purpose: To investigate the association between stereoacuity and suppression during occlusion therapy for patients with anisometropic amblyopia. Design: Retrospective study. Patients and Methods: This study included 19 patients with hyperopic anisometropic amblyopia who underwent occlusion therapy. The mean age of the patients was 5.5 ± 1.4 years. The participants were evaluated for improvement in stereoacuity and suppression before beginning occlusion therapy, when the highest amblyopic visual acuity (VA) was achieved, during tapering, at the end of occlusion therapy, and at the final visit. Stereoacuity was evaluated using the TNO test or JACO stereo test. The presence of suppression was evaluated using circle No. 1 of the Stereo Fly Test or JACO results as the optotype. Results: Of the 19 patients, 13 (68.4%) had suppression before occlusion, eight (42.1%) when the highest VA was achieved, five (26.3%) during tapering, and none at the final visit. Of the 13 patients with suppression before occlusion, 10 (76.9%) showed further improvement in stereoacuity when suppression disappeared, and nine had foveal stereopsis of 60 arcseconds. A significant association was confirmed between foveal stereopsis and suppression when the highest VA was achieved and during the tapering period (P<0.05, Fisher's exact test). Conclusion: Suppression was observed even when the VA in amblyopic eyes reached the highest score. By gradually decreasing the duration of occlusion, suppression was eliminated, leading to the acquisition of foveal stereopsis.

Disturbances in the ocular surface microbiome by perioperative antimicrobial eye drops.

We aimed to elucidate the effects of antimicrobial eye drops used in the perioperative period of ophthalmic surgery on the ocular surface microbiome by metagenomic analysis. Twenty-eight eyes from 15 patients (mean age 74.1 years) with no history of eye drop use within 3 months before cataract surgery were included in this study. Gatifloxacin eye drops were used in all patients in the perioperative period. The antimicrobial eye drops were started 3 days before surgery. They were discontinued after conjunctival sac specimen collection for 2 weeks after the surgery. Conjunctival sac specimens were collected to investigate the alterations in the ocular surface microbiome by meta-16S analysis targeting the V3-V4 region of the bacterial 16S rRNA gene. Principal coordinate analysis showed that the bacterial composition tended to be different before and 2 and 4 weeks after surgery. Individual observations on six eyes showed that the bacterial composition at 12 weeks after surgery was closer to that before surgery than to that at 4 weeks after surgery in two eyes, while the bacterial composition in the remaining four eyes was different at various time points. Before surgery, Firmicutes, Proteobacteria, and Bacteroidetes were predominant; however, 2 weeks after surgery, the proportion of Proteobacteria increased and that of Firmicutes decreased. A similar trend was noticed 4 weeks after surgery, although antibacterial eye drops had been discontinued 2 weeks after surgery. The Shannon-Weaver coefficient showed a decreasing trend at 2-, 4-, and 12-weeks post operation compared to that before operation. The diversity of the microbiome decreased significantly at 2- and 4-weeks after surgery when compared to that before surgery (p < 0.05). The ocular surface microbiome is easily disrupted by antimicrobial eye drops, and it needs recovery time. In such cases, the ocular surface microbiome is presumed to contain many antimicrobial-resistant bacteria. In some cases, it may not recover, and a new microbiome is formed.

Surgical treatment of traction retinal detachment associated with compound heterozygous congenital protein C deficiency.

Purpose: Congenital protein C deficiency leads to a prothrombotic state that may result in potentially sight- and life-threatening thromboembolic attacks. In this report, we report two cases of infants with compound heterozygous protein C deficiency who underwent lensectomies and vitrectomies for the treatment of traction retinal detachments (TRDs). Observations: One two-month-old and one three-month-old female neonates with leukocoria and purpura fulminans received a diagnosis of protein C deficiency and were referred to ophthalmology. In both cases, the right eye had a total retinal detachment that was considered inoperable, while the left eye had a partial TRD for which surgery was performed. Of the two operated eyes, one resulted in a total retinal detachment, while the other eye has remained stable with no retinal detachment progression three months after surgery. Conclusions: Compound heterozygous congenital protein C deficiency may lead to the rapid development of severe TRDs with poor visual and anatomical prognoses. Early diagnosis and surgery for the treatment of partial TRDs with low disease activity may help prevent progression towards total retinal detachments in these infants.

Avascular Peripheral Retina in Infants.

Avascular peripheral retina in an infant is a common characteristic of numerous pediatric retinal vascular disorders and often presents a diagnostic challenge to the clinician. In this review, key features of each disease in the differential diagnosis, from retinopathy of prematurity, familial exudative vitreoretinopathy, Coats disease, incontinentia pigmenti, Norrie disease, and persistent fetal vasculature, to other rare hematologic conditions and telomere disorders, will be discussed by expert ophthalmologists in the field.