Mice with deficiency in Pcdh15, a gene associated with bipolar disorders, exhibit significantly elevated diurnal amplitudes of locomotion and body temperature.

Genetic factors significantly affect the pathogenesis of psychiatric disorders. However, the specific pathogenic mechanisms underlying these effects are not fully understood. Recent extensive genomic studies have implicated the protocadherin-related 15 (PCDH15) gene in the onset of psychiatric disorders, such as bipolar disorder (BD). To further investigate the pathogenesis of these psychiatric disorders, we developed a mouse model lacking Pcdh15. Notably, although PCDH15 is primarily identified as the causative gene of Usher syndrome, which presents with visual and auditory impairments, our mice with Pcdh15 homozygous deletion (Pcdh15-null) did not exhibit observable structural abnormalities in either the retina or the inner ear. The Pcdh15-null mice showed very high levels of spontaneous motor activity which was too disturbed to perform standard behavioral testing. However, the Pcdh15 heterozygous deletion mice (Pcdh15-het) exhibited enhanced spontaneous locomotor activity, reduced prepulse inhibition, and diminished cliff avoidance behavior. These observations agreed with the symptoms observed in patients with various psychiatric disorders and several mouse models of psychiatric diseases. Specifically, the hyperactivity may mirror the manic episodes in BD. To obtain a more physiological, long-term quantification of the hyperactive phenotype, we implanted nano tag® sensor chips in the animals, to enable the continuous monitoring of both activity and body temperature. During the light-off period, Pcdh15-null exhibited elevated activity and body temperature compared with wild-type (WT) mice. However, we observed a decreased body temperature during the light-on period. Comprehensive brain activity was visualized using c-Fos mapping, which was assessed during the activity and temperature peak and trough. There was a stark contrast between the distribution of c-Fos expression in Pcdh15-null and WT brains during both the light-on and light-off periods. These results provide valuable insights into the neural basis of the behavioral and thermal characteristics of Pcdh15-deletion mice. Therefore, Pcdh15-deletion mice can be a novel model for BD with mania and other psychiatric disorders, with a strong genetic component that satisfies both construct and surface validity.

Decrease in electrolyte after vitrectomy surgery may affect the results of forensic investigations using vitreous humor.

PURPOSE: Vitreous humor (VH) is used for postmortem biochemical studies because it is well protected in an uncontaminated state even after death. The goal of this research was to investigate electrolyte concentrations in the VH from human eyes with and without a history of vitrectomy surgery. METHODS: We analyzed the sodium (Na), potassium (K), chloride (Cl) and magnesium (Mg) concentrations from 34 VH samples from 34 patients. Eleven samples were from eyes with a history of vitrectomy, and the remaining 23 eyes had no history of vitrectomy. The correlations of Na, K, Cl and Mg concentrations with patient age, interval between first and second vitrectomy, and lens status (history of cataract surgery) were also evaluated. RESULTS: The Na, K, Cl and Mg concentrations in VH from vitrectomized eyes were 134.1 ± 7.9 mmol/L, 3.7 ± 0.2 mmol/L, 99.7 ± 6.7 mmol/L and 0.59 ± 0.09 mmol/L, respectively; all were significantly lower than the corresponding concentrations in VH from control eyes (lower by 5.0%, 11.0%, 11.7%, and 22.6%, respectively). Na, K, Cl and Mg concentrations in VH from vitrectomized eyes did not show significant correlations with patient ages or the interval between their first and second vitrectomies. There were no significant differences in Na, K, Cl and Mg concentrations in VH between phakic eyes and intraocular lens-implanted eyes. CONCLUSIONS: With the increasing number of vitrectomies being performed, it is necessary to consider the history of vitrectomy when using a subject's VH in forensic examination.

Secondary Angle Closure Caused by Anterior Displacement of Capsular Tension Ring and Intraocular Lens Due to Aqueous Misdirection.

A capsular tension ring (CTR) is used for support to stabilize the capsular bag and intraocular lens (IOL) during and after cataract surgery. Although complications involving the CTR-IOL complex are not uncommon, cases of anterior displacement leading to complications are rare. This report presents a case of secondary angle closure caused by anterior displacement of the CTR-IOL complex due to aqueous misdirection and reports unique findings noted on anterior segment optical coherence tomography (AS-OCT). The patient, a 69-year-old woman, developed an acute angle closure crisis (AACC) and underwent cataract surgery with the implantation of a CTR and IOL. Post-surgery, there was an improvement in the central depth of the anterior chamber, but the patient experienced intermittent spikes in intraocular pressure. AS-OCT revealed a flat center of the iris and a closed anterior chamber angle which are plateau-iris-like findings. Secondary angle closure was caused by the CTR-IOL complex which was anteriorly displaced and pushed the peripheral iris owing to aqueous misdirection syndrome. Three weeks after the initial surgery, the patient underwent CTR removal, anterior vitrectomy, and intrascleral lens fixation. After the second surgery, intraocular pressure was normalized without any medications, and the anterior chamber angle was enlarged. This case provides a better understanding of secondary angle closure caused by the anterior displacement of the CTR-IOL complex and highlights the importance of AS-OCT in the detection of such complications.

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.

Detection of elusive DNA copy-number variations in hereditary disease and cancer through the use of noncoding and off-target sequencing reads.

Copy-number variants (CNVs) play a substantial role in the molecular pathogenesis of hereditary disease and cancer, as well as in normal human interindividual variation. However, they are still rather difficult to identify in mainstream sequencing projects, especially involving exome sequencing, because they often occur in DNA regions that are not targeted for analysis. To overcome this problem, we developed OFF-PEAK, a user-friendly CNV detection tool that builds on a denoising approach and the use of "off-target" DNA reads, which are usually discarded by sequencing pipelines. We benchmarked OFF-PEAK on data from targeted sequencing of 96 cancer samples, as well as 130 exomes of individuals with inherited retinal disease from three different populations. For both sets of data, OFF-PEAK demonstrated excellent performance (>95% sensitivity and >80% specificity vs. experimental validation) in detecting CNVs from in silico data alone, indicating its immediate applicability to molecular diagnosis and genetic research.

INCIDENCE AND RISK FACTORS OF INTRAOCULAR INFLAMMATION AFTER BROLUCIZUMAB TREATMENT IN JAPAN: A Multicenter Age-Related Macular Degeneration Study.

PURPOSE: To investigate the incidence of intraocular inflammation (IOI) and its risk factors following intravitreal injections of brolucizumab for neovascular age-related macular degeneration in Japan. METHODS: A total of 1,351 Japanese consecutive patients with neovascular age-related macular degeneration who were treated with brolucizumab from May 2020 to May 2022 at 14 institutions were examined. The variables analyzed were the number of brolucizumab injections, time to onset of IOI, and risk factors. RESULTS: Intraocular inflammation developed in 152 eyes (11.3%). Retinal vasculitis and/or retinal occlusion occurred in 53 eyes (3.9%). Ninety-four patients received bilaterally, bilateral IOI occurred in five patients (5.3%). Sixteen eyes (1.2%) had irreversible visual acuity loss and nine eyes (0.67%) had visual loss of three lines or more due to retinal vasculitis and/or retinal occlusion. The cumulative IOI incidence was 4.5%, 10.3%, and 12.2% at 30, 180, and 365 days (1-year), respectively. History of IOI (including retinal vasculitis) and/or retinal occlusion (odds ratio [OR], 5.41; P = 0.0075) and female sex (OR, 1.99; P = 0.0004) were significantly associated with IOI onset. CONCLUSION: The 1-year cumulative incidence of IOI in Japanese neovascular age-related macular degeneration patients treated with brolucizumab was 12.2%. History of IOI (including retinal vasculitis) and/or retinal occlusion and female sex were significant risk factors.

Association Between Torque Teno Virus and Systemic Immunodeficiency in Patients With Uveitis With a Suspected Infectious Etiology.

PURPOSE: To determine the correlation between the presence of torque teno virus (TTV) in the aqueous humor of patients with uveitis and clinical information, including immunodeficiency history. DESIGN: Multicenter, retrospective, cross-sectional study. METHODS: Fifty-eight patients with uveitis with a suspected infectious etiology and 24 controls with cataract or age-related macular degeneration were included. We used quantitative polymerase chain reaction to test all subjects for TTV and multiplex polymerase chain reaction to test uveitis subjects for common ocular pathogens. When possible, both serum and aqueous humor samples were tested. Ocular TTV positivity was compared with age, sex, and a history of systemic immunodeficiency with logistic analysis. RESULTS: Ocular TTV positivity was found in 23%, 11%, and 0% of patients with herpetic uveitis, nonherpetic uveitis, and controls, respectively. Among patients with herpes infection, positivity for ocular TTV was found in 43%, 8%, 14%, and 50% of patients with cytomegalovirus retinitis, iridocyclitis, acute retinal necrosis, and Epstein-Barr virus-positive uveitis, respectively. Patients with cytomegalovirus retinitis showed a significantly higher rate of ocular TTV infection than controls (P = .008). Serum analysis revealed TTV positivity in 90% of patients with uveitis and in 100% of controls. Age- and gender-adjusted logistic analysis revealed a correlation between ocular TTV positivity and systemic immunodeficiency (P = .01), but no correlations between ocular TTV and age, gender, or viral pathogenic type. CONCLUSIONS: These findings suggest that positivity for ocular TTV was correlated with a clinical history of systemic immunodeficiency.

Assessment of factors affecting flicker ERGs recorded with RETeval from data obtained from health checkup screening.

PURPOSE: To determine the factors significantly associated with the amplitudes and implicit times of the flicker electroretinograms (ERGs) recorded with the RETeval system by analyzing the comprehensive data obtained during a health checkup screening. METHODS: Flicker ERGs were recorded with the RETeval system from 373 individuals who had a normal fundus and optical coherence tomography images. The sex, age, anthropometric, ophthalmologic, and hematologic data were collected from all participants who were 40- to 89-years-of-age. Univariable and multivariable linear mixed effects regression analyses were performed to identify factors that were significantly associated with the implicit times and amplitudes of the RETeval flicker ERGs. RESULTS: Univariable linear mixed effects regression analysis showed significant correlations between the implicit times and the best-corrected visual acuity, the age, the axial length, the blood sugar level, and the blood urea nitrogen level. Analyses by multivariable linear mixed effects regression identified that the axial length (ß = 0.28), the age (ß = 0.24), and the blood sugar level (ß = 0.092) were three independent factors that were significantly correlated with the implicit times of the RETeval flicker ERGs. Univariable linear mixed effects regression analysis also showed significant correlations between the amplitudes of the RETeval flicker ERGs and the age, the platelet count, and the creatinine level. Multivariable linear mixed effects regression models identified the age (ß = -0.092), the platelet count (ß = 0.099), and the creatinine level (ß = -0.12) as three independent factors that were significantly correlated with the amplitudes of the RETeval flicker ERGs. However, the smoking habits, body mass index, and the blood pressure were not significantly correlated with either the implicit times or amplitudes of the RETeval flicker ERGs. CONCLUSIONS: Our results indicate that the age and some ophthalmologic and hematologic findings but not the anthropometric findings were significantly associated with the implicit times and amplitudes of the RETeval flicker ERGs. Thus, clinicians should remember these factors when analyzing the RETeval flicker ERGs.

LONG-TERM MORPHOLOGIC CHANGES IN MACULAR NEOVASCULARIZATION UNDER AFLIBERCEPT TREATMENT WITH A TREAT-AND-EXTEND REGIMEN.

PURPOSE: To examine the morphologic changes in macular neovascularization (MNV) secondary to age-related macular degeneration after 2 years of aflibercept treatment under a treat-and-extend (T&E) regimen. METHODS: This retrospective study analyzed the medical records for 26 eyes of 25 patients diagnosed with treatment-naive neovascular age-related macular degeneration and treated with aflibercept under a treat-and-extend regimen for 2 years. The areas of the MNV and vascular structures were assessed using swept-source optical coherence tomography angiography at baseline and after 2 years of treatment. RESULTS: The mean MNV area increased significantly from 0.65 ± 0.42 mm 2 at baseline to 0.78 ± 0.45 mm 2 at 2 years. At 2 years, the mean change in the MNV area from baseline was 22% (interquartile range: 4%-60%). The baseline MNV area was negatively correlated with the change ratio of the MNV areas at 2 years and baseline ( R = -0.68, P < 0.001). Nine of the 26 eyes (34.6%) showed newly formed mature vessels, and 7 eyes (26.9%) showed prominently developing preexisting mature vessels. CONCLUSION: Macular neovascularization expanded and showed vascular maturation under aflibercept treatment with a treat-and-extend regimen. The smaller the MNV at baseline, the greater is its expansion in 2 years.

Genome-Wide Association Study of Age-Related Macular Degeneration Reveals 2 New Loci Implying Shared Genetic Components with Central Serous Chorioretinopathy.

PURPOSE: To investigate the genetic architecture of age-related macular degeneration (AMD) in a Japanese population. DESIGN: Genome-wide association study (GWAS). PARTICIPANTS: Three thousand seven hundred seventy-two patients with AMD and 16 770 control participants from the Japanese population were enrolled in the association analyses. METHODS: We conducted a meta-analysis of 2 independent GWASs that included a total of 2663 patients with AMD and 9471 control participants using the imputation reference panel for genotype imputation specified for the Japanese population (n = 3541). A replication study was performed using an independent set of 1109 patients with AMD and 7299 control participants. MAIN OUTCOME MEASURES: Associations of genetic variants with AMD. RESULTS: A meta-analysis of the 2 GWASs identified 6 loci significantly associated with AMD (P < 5.0 × 10-8). Of these loci, 4 were known to be associated with AMD (CFH, C2/FB, TNFRSF10A, and ARMS2), and 2 were novel (rs4147157 near WBP1L and rs76228488 near GATA5). The newly identified associations were confirmed in a replication study (P < 0.01). After the meta-analysis of all datasets, we observed strong associations in these loci (P = 1.88 × 10-12 and P = 1.35 × 10-9 for meta-analysis for rs4147157 and rs76228488, respectively). When we looked up the associations in the reported central serous chorioretinopathy (CSC) GWAS conducted in the Japanese population, both loci were associated significantly with CSC (P = 4.86 × 10-3 and P = 4.28 × 10-3 for rs4147157 and rs76228488, respectively). We performed a genetic colocalization analysis for these loci and estimated that the posterior probabilities of shared causal variants between AMD and CSC were 0.39 and 0.60 for WBP1L and GATA5, respectively. Genetic correlation analysis focusing on the epidemiologically suggested clinical risk factors implicated shared polygenic architecture between AMD and smoking cessation (rg [the measure of genetic correlation] = -0.33; P = 0.01; false discovery rate, 0.099). CONCLUSIONS: Our findings imply shared genetic components conferring the risk of both AMD and CSC. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Choroidal hemodynamics in central serous chorioretinopathy after half-dose photodynamic therapy and the effects of smoking.

This retrospective study aimed to evaluate choroidal hemodynamics after half-dose photodynamic therapy (PDT) for central serous chorioretinopathy (CSC) and the effects of smoking using laser speckle flowgraphy. This study included 29 eyes of 29 patients treated with half-dose PDT for CSC, who were followed-up for at least 6 months. The mean blur rate (MBR) in the PDT irradiation area (whole area), the pachyvessel (PV) area, non-PV (NPV) area, and filling delay (FD) area were assessed at baseline and 1, 3, and 6 months post-PDT, respectively. The MBR was also assessed by smoking status. The MBR significantly decreased from baseline in the whole, PV, NPV, and FD areas at all time points (P < 0.001). Of the 29 patients, 6 were never smokers, 13 were past smokers, and 10 were current smokers. At baseline, no significant difference was found in the MBR in the whole, PV, NPV, and FD areas among never, past, and current smokers. The MBR changes showed a significantly smaller decrease in current smokers than in never smokers in the whole (P = 0.021), PV (P = 0.009), and NPV (P = 0.034) areas, but not in the FD area (P = 0.172). Half-dose PDT for CSC reduced choroidal blood flow in the PDT-irradiated area, which was blunted by current smoking status.

Accuracy of pattern deviation in estimating the glaucomatous damage in the central 10° visual field in eyes with glaucoma and cataract.

BACKGROUND/AIMS: The accuracy of pattern deviation (PD) in estimating the damage to the glaucomatous visual field (VF) in the central 10° in eyes with glaucoma and cataract is unclear. METHODS: This retrospective study includes 63 eyes of 52 glaucoma patients who successfully underwent cataract surgery or cataract surgery plus iStent implantation. Using the Humphrey Field Analyser 10-2 test, VF was measured within 6 months preoperatively and postoperatively (VFpre and VFpost, respectively). The mean total deviation values in VFpost (mTDpost) indicates glaucomatous damage without cataract and the difference between this value and mean PD values in VFpre (mPDpre) was evaluated (εmPD). The effect of cataract was then evaluated as the difference between mTDpost and mTDpre (ΔmTD), while the effects of mTDpost and ΔmTD on εmPD were also assessed. In addition, based on preoperative visual acuity (VApre) and VFpre, the optimal model for predicting mTDpost was identified. The error of this method (εOptimalModel) was estimated as the difference against mTDpost, which was compared with εmPD. RESULTS: Compared with mTDpre, there was a significant improvement in mTDpost (p=0.028). A significant difference was observed between mPDpre and mTDpost (p<0.001). Further, εmPD significantly increased with the increase of mTDpost or ΔmTD (p<0.001 and p=0.0444, respectively). The absolute εOptimalModel was significantly smaller than the absolute εmPD (p<0.001). CONCLUSIONS: This study warns clinicians that PD of the central 10° VF might underestimate the glaucomatous VF damage with the progression of glaucoma and overestimate it as a cataract progresses.

Surgical outcome and pathological findings in macular epiretinal membrane caused by neurofibromatosis type 2.

We present surgical outcomes in a 10-year-old Japanese girl with neurofibromatosis type 2 (NF2)-induced epiretinal membrane (ERM). Her right eye underwent lens-sparing 27-gauge microincision vitrectomy surgery (MIVS) with ERM peeling. Decimal best-corrected visual acuity increased from 0.3 to 0.4 postoperatively. However, abnormal thickening of the macula persisted for 3 years. Staining of the extracted ERM revealed many cells positive for glial fibrillary acidic protein and nestin. Although removal of NF2-induced ERM with MIVS can improve visual acuity, the potential surgical risks require careful consideration on a case-by-case basis.

Switching from aflibercept to brolucizumab for the treatment of refractory neovascular age-related macular degeneration.

PURPOSE: To examine the 16-week outcomes of switching to brolucizumab in eyes with neovascular age-related macular degeneration (nAMD) refractory to aflibercept. STUDY DESIGN: Retrospective observational study. METHODS: Data of eyes with nAMD who switched to brolucizumab because of resistance to aflibercept were collected. The best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution), central retinal thickness (CRT), central choroidal thickness (CCT), and exudative status on optical coherence tomography were analyzed. RESULTS: A total of 48 eyes of 48 patients were reviewed. At 4 to 7 weeks after switching, BCVA changed from 0.26 ± 0.19 to 0.25 ± 0.21 (not significant; P = 0.95), but CRT significantly decreased from 298.9 ± 108.4 µm to 241.9 ± 92.5 µm (P < 0.001) and CCT from 182.6 ± 89.3 µm to 169.7 ± 82.6 µm (P < 0.001). Of the 23 eyes refractory to monthly aflibercept injections, 12 (52.2%) achieved a dry macula, and 8 (34.8%) reduced exudative changes at 1 month. At 16 weeks, 31 eyes (64.6%) achieved the treatment interval ≥ 8 weeks. Two patients (4.2%) dropped out, 7 eyes (14.6%) developed intraocular inflammation (IOI), and 8 eyes (16.7%) switched back to aflibercept because of the failure to extend the treatment interval ≥ 8 weeks. CONCLUSION: Switching to brolucizumab in eyes refractory to aflibercept conferred favorable outcomes in controlling exudative changes. However, IOI and the regulation of the treatment interval to at least 8 weeks during the maintenance phase disrupted the continuation of brolucizumab treatment.

Polypoidal choroidal vasculopathy in a case of retinitis pigmentosa, successfully treated with intravitreal aflibercept.

PURPOSE: Polypoidal choroidal vasculopathy (PCV) is a subtype of age-related macular degeneration that is seen frequently in Asians. Nevertheless, it is rare for this condition to be combined with retinitis pigmentosa (RP). The purpose of this paper is to present findings from this rare combination in a Japanese patient, and to describe its successful treatment with intravitreal aflibercept (IVA). OBSERVATIONS: The patient was a 71-year-old Japanese woman with RP (diagnosed at the age of 30) and PCV. She noticed a decrease in vision in her right eye 6 months previously. Decimal best-corrected visual acuity (BCVA) was 0.05 in her right eye. Optical coherence tomography and indocyanine green angiography (IA) revealed serous retinal detachment (SRD) and PCV in her right eye. The SRD was initially resolved after 3 monthly treatments with IVA, but recurrences began 5 months later, requiring four more treatments with IVA, performed about every 4 months within the next 12 months, for successful resolution. There were no recurrences of PCV in 7 more months of follow-up, as confirmed with IA at the final appointment. Final decimal BCVA in the right eye improved to 0.15. Furthermore, macular retinal sensitivity, measured with microperimetry, increased after the treatment, and RP-related visual field narrowing, determined by Goldmann perimetry, did not progress throughout follow up of 26 months. CONCLUSION: More than 2 years of follow up showed that IVA may be effective for treating PCV, even in RP patients, and can increase central visual function without causing progression of RP-related visual field narrowing.

Ocular microcirculation changes, measured with laser speckle flowgraphy and optical coherence tomography angiography, in branch retinal vein occlusion with macular edema treated by ranibizumab.

PURPOSE: This study searched for early predictive vascular biomarkers for visual outcomes in eyes with macular edema caused by branch retinal vein occlusion (BRVOME). METHODS: Twenty-four eyes of 24 subjects with BRVOME were treated with the intravitreal injection of ranibizumab (IVR) for at least 6 months. We measured mean blur rate (MBR) in the optic nerve head (ONH) and vessel density (VD) in the macula with laser speckle flowgraphy and optical coherence tomography angiography, respectively. RESULTS: Six-month post-IVR best-corrected visual acuity (BCVA) was correlated positively with age, pre-IVR BCVA, 1-month post-IVR BCVA, 3-month post-IVR BCVA and pre-IVR systolic blood pressure (P < 0.001, P < 0.001, P < 0.001, P < 0.001 and P = 0.02, respectively) and negatively with pre-IVR overall MBR, 1-month post-IVR overall MBR, 6-month post-IVR overall MBR, 3-month post-IVR deep retinal capillary plexus (DCP) VD and 6-month post-IVR DCP VD (P = 0.03, P = 0.03, P = 0.02, P = 0.01 and P = 0.005, respectively). Furthermore, a multiple regression analysis showed that pre-IVR overall MBR (ß = - 0.67, P = 0.009) was among independent prognostic factors predicting 6-month post-IVR BCVA. Six-month post-IVR DCP VD was also correlated with overall MBR at all time points. CONCLUSION: ONH blood flow may be a pre-IVR biomarker of both visual outcomes and post-IVR deep macular microcirculation in eyes with BRVOME.

RETINAL SENSITIVITY AND VESSEL DENSITY AFTER MACULAR HOLE SURGERY WITH THE SUPERIOR INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE.

PURPOSE: To evaluate retinal vessel density and retinal sensitivity (RS) after macular hole surgery with the superior inverted internal limiting membrane flap technique. METHODS: Retrospective, observational case series. Twenty-one patients with idiopathic macular hole underwent 27-gauge vitrectomy with the superior inverted internal limiting membrane flap technique and triamcinolone acetonide. Measurements included RS, which was measured with microperimetry, as well as retinal vessel density in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), which was measured with optical coherence tomography angiography. All parameters were evaluated in the superior and inferior sectors of the macula preoperatively and 1, 3, and 6 months postoperatively. RESULTS: Six months postoperatively, retinal thickness in the inferior sector was unchanged, but retinal thickness in the superior sector decreased significantly (P < 0.01). SCP vessel density in both sectors was unchanged at all postoperative time points. DCP vessel density in both sectors increased very significantly at 3 months (P < 0.01) and returned to baseline at 6 months. RS in the inferior sector increased by 47% 3 months postoperatively and by 61% 6 months postoperatively (P < 0.05 and P < 0.001, respectively), but RS in the superior sector increased only at 6 months postoperatively and only by 22% (P < 0.05). CONCLUSION: Lower recovery of RS in the superior sector suggests that internal limiting membrane peeling might affect the postoperative visual function.

Successful surgical outcomes after 23-, 25- and 27-gauge vitrectomy without scleral encircling for giant retinal tear.

PURPOSE: Retinal detachment due to giant retinal tears (GRTs), tears larger than 90°, is rare and difficult to treat. Here, we show and compare surgical results of 23-, 25- and 27-gauge (G) micro-incision vitrectomy surgery (MIVS) for GRT. STUDY DESIGN: Retrospective and interventional case series. METHODS: Retrospective review of 41 eyes of 38 patients with GRT who underwent MIVS. Surgical outcomes after MIVS, including reattachment rates and postoperative complications, were compared between instrument gauges. All patients were followed for at least 6 months postoperatively. RESULTS: MIVS with 23G, 25G and 27G instruments was performed in 7, 19 and 15 eyes, respectively. Silicone oil (SO) was used in 34 of 41 eyes (83%) with a mean removal time of 43.8 days after first surgery. Best-corrected visual acuity (BCVA) was recovered or maintained in 39 eyes (95%). Reattachment was attained after initial surgery in 38 of 41 eyes (93%) (23G: 6/7 [86%]; 25G: 17/19 [89%]; 27G: 15/15 [100%]). Final reattachment was eventually achieved in all eyes (two eyes needed support from scleral encircling). Postoperative complications occurred in 16 eyes (39%) (23G: 3/7 [43%]; 25G: 8/19 [42%]; 27G: 5/15 [33%]), including macular pucker, cystoid macular edema, macular hole, subretinal perfluorocarbon liquid, retinal folds, vitreous hemorrhage and redetachment. There were no significant differences between the three groups in rate of high myopia, GRT size, operation time, phacovitrectomy rate, SO usage rate, initial reattachment rate, final reattachment rate, preoperative BCVA, final BCVA or rate of postoperative complications. CONCLUSION: Despite occasional postoperative complications, primary MIVS, regardless of gauge size, appears to be a safe and feasible option for GRT surgery.

Association of retinal vessel density with retinal sensitivity in surgery for idiopathic epiretinal membrane.

PURPOSE: The success of surgical treatment for idiopathic epiretinal membrane (ERM) is measured by postoperative best-corrected visual acuity (BCVA), metamorphopsia, and foveal retinal sensitivity (RS).This study searched for predictive biomarkers of surgical success by determining the association between foveal RS and various aspects of vessel density (VD) in the fovea of patients with ERM. METHODS: The study examined 25 eyes of 25 patients with ERM who underwent 27-gauge microincision vitrectomy surgery (MIVS). RS was measured with microperimetry (MP-3; NIDEK) at four central points in the fovea with an interpoint distance of 2°. VD was measured with SD-OCT (RS 3000; NIDEK) within the 1-mm2 square defined by the 4 RS points at various depths, including the superficial and deep retinal capillary plexus (SCP and DCP, respectively). RESULTS: Though VD did not change throughout the follow-up period, BCVA and RS significantly improved 1 and 3 months after surgery, respectively (both P < 0.0017). Postoperative RS at 6 months was positively correlated with postoperative DCP VD at 1, 3, and 6 months (r = 0.62, P = 0.001; r = 0.40, P = 0.049; r = 0.53, P = 0.007, respectively), but not with SCP VD at any time point. Multiple regression analysis confirmed that postoperative RS at 6 months was associated with postoperative DCP VD at 1 month (P = 0.03). CONCLUSION: Higher postoperative DCP VD at 1 month contributed to better postoperative foveal RS at 6 months. Early postoperative VD in the fovea might be a useful predictive biomarker of late postoperative RS in the fovea in ERM patients.

Endogenous endophthalmitis caused by group B streptococcus; case reports and review of 35 reported cases.

BACKGROUND: Group B streptococcus (GBS), a gram-positive coccus that occasionally causes neonatal sepsis or invasive infection in the elderly, has been considered a rare cause of endogenous bacterial endophthalmitis (EBE). However, the number of invasive GBS infections is increasing, particularly in elderly patients with underlying conditions such as diabetes mellitus (DM), cardiovascular disease and cancer. We report 6 cases of EBE caused by GBS and review the literature. METHODS: Retrospective case series and literature review. RESULTS: In the current case series, 6 eyes of 6 patients developed EBE caused by GBS. The average age was 73.5 years. The focus of infection included the urinary tract, cellulitis, arthritis, peritonitis, catheter-associated infection and endocarditis. Four patients had DM. While all 6 strains were sensitive to ß-lactams (penicillins and cephems), 4 strains were resistant to levofloxacin (no data for 1 isolate). Each case was treated with the systemic antibiotic to which the individual strain was sensitive. All cases showed poor visual acuity at presentation (decimal visual acuity: less than 0.03). Vitrectomy with intravitreal antibiotics injection was performed in 4 cases. Visual acuity recovered in 4 cases and did not recover in 2 cases, even after vitrectomy. The literature review of 53 eyes of 41 patients revealed that 60% of eyes finally lost all vision, and death occurred in 2 cases. Initial visual acuity of less than counting fingers was associated with a final outcome of lost vision. Of 41 patients, 13 (32%) had DM as an underlying medical condition. The most common extra-ocular infection focus was endocarditis (37%). CONCLUSIONS: DM is common in patients with EBE caused by GBS. While the 4 cases in the current report had a relatively good visual acuity outcome, despite poor initial visual acuity, the literature review indicated that EBE caused by GBS is generally a severe condition with a poor prognosis. The current study also indicates the importance of considering the possibility of endocarditis on encountering EBE caused by GBS.