Surgical outcomes of endoscopic dacryocystorhinostomy for eyes with nasolacrimal duct obstruction via tear meniscus height evaluation.

PURPOSE: To evaluate the association of tear meniscus height (TMH) with clinical outcomes of patients who underwent endonasal dacryocystorhinostomy. METHODS: We recruited 304 patients from two institutes. The TMH was measured using anterior segment optical coherence tomography before surgery. All patients underwent endoscopic DCR with lacrimal intubation stent insertion. The lacrimal stent was removed 2 months after surgery. The TMH was measured at 2 months and 12 months after surgery. Improvements in epiphora were assessed using a visual analogue scale (range, 0-2). Recurrence was determined based on lacrimal irrigation and endoscopic evaluation results. RESULTS: All patients experienced improvements in subjective symptoms 2 months after surgery. The mean TMH also decreased significantly compared with that before surgery. During the follow-up period, four patients experienced recurrence. The mean TMH 12 months after surgery was significantly lower than that before surgery. The rate of change in the TMH was significantly associated with the use of a dacryoendoscope during sheath-guided lacrimal stent intubation at all time points. Of the 251 patients who were followed up at 12 months after surgery, three reported recurrences, and 17 reported mild improvement of epiphora. The rate of change in the TMH was significantly associated with epiphora improvement. Height was also associated with epiphora improvement. CONCLUSIONS: Endoscopic DCR is an acceptable surgical procedure for managing nasolacrimal duct obstruction. Sheath-guided lacrimal stent intubation using a dacryoendoscope resulted in a greater reduction in postoperative TMH compared to the blind insertion technique, which may lead to favorable clinical outcomes.

Effectiveness of Reduced-fluence Photodynamic Therapy for Chronic Central Serous Chorioretinopathy: A Propensity Score Analysis.

Purpose: To investigate the 2-year effectiveness of reduced-fluence photodynamic therapy (rf-PDT) for chronic central serous chorioretinopathy (cCSC). Design: Retrospective cohort study. Participants: A total of 223 consecutive patients with newly diagnosed cCSC with active serous retinal detachment (SRD) were included from May 2007 to June 2017 and followed up for at least 2 years. Patients who underwent ocular treatment other than cataract surgery before the beginning of recruitment and those who had macular neovascularization at baseline were excluded. Methods: All patients underwent a comprehensive ophthalmic evaluation, including measurements of best-corrected visual acuity (BCVA), slit-lamp examination, dilated fundus examination, color fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and spectral-domain OCT. An inverse probability of treatment weighting (IPTW) methodology was applied to balance 18 baseline characteristics between patients who received rf-PDT (rf-PDT group) and those who did not receive treatment (controls). Inverse probability of treatment weighting survival analysis and regression were performed. Main Outcome Measures: The proportion of patients whose BCVA at 24 months was the same or improved compared with the baseline visual acuity (VA) (VA maintenance rate). Results: A total of 155 eyes (rf-PDT group: 74; controls: 81) were analyzed. The patients' backgrounds were well balanced after IPTW with standardized differences of < 0.10. An IPTW regression analysis revealed that the VA maintenance rate was significantly higher in the rf-PDT group than in the controls (93.6% vs. 70.9%, P < 0.001, 12 months; 85.7% vs. 69.8%, P = 0.019, 24 months). The rf-PDT group tended to show better VA improvement, but was not statistically significant (-0.06 vs. -0.008, P = 0.07, 12 months; -0.06 vs. -0.03, P = 0.32, 24 months). An IPTW Cox regression showed a significantly higher rate of complete SRD remission in the rf-PDT group (hazard ratio, 5.05; 95% confidence interval, 3.24-7.89; P < 0.001). Conclusions: The study suggests the beneficial effect of rf-PDT for cCSC for both VA maintenance and higher proportion of complete SRD remission in the clinical setting.

Association between central serous chorioretinopathy susceptibility genes and choroidal parameters.

PURPOSE: To evaluate the association between central serous chorioretinopathy (CSC) susceptibility genes and choroidal parameters in a large Japanese cohort. STUDY DESIGN: Retrospective cohort study. METHODS: Of the 9850 individuals in the Nagahama study whose second visit was between 2013 and 2016, those with optical coherence tomography (OCT) images with enhanced depth imaging (EDI), axial length, and genome-wide single nucleotide polymorphism (SNP) genotyping data were included. We calculated subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), normalized choroidal intensity (NCI), and vertical asymmetry of choroidal thickness. Genome-wide quantitative trait locus (QTL) analyses were performed for each parameter. We screened for four CSC susceptibility SNPs: CFH rs800292, TNFRSF10A rs13278062, GATA5 rs6061548, and VIPR2 rs3793217. Whenever an SNP was not included in the genotyping data after quality control, its proxy SNP was selected. RESULTS: In total, 4586 participants were evaluated. CFH rs800292 was significantly associated with SFCT (P < 0.001) and CVI (P < 0.001). VIPR2 rs3793217 was significantly associated with SFCT (P < 0.001) but not with CVI. Whereas, TNFRSF10A rs13254617 and GATA5 rs6061548 were not significantly associated with SFCT or CVI. None of these SNPs was associated with NCIEDI and asymmetry of choroidal thickness. CONCLUSION: CFH, VIPR2, TNFRSF10A, and GATA5 showed different association patterns with choroidal parameters. Although the mechanism of CSC pathogenesis by choroidal changes is not fully understood, this finding suggests that each gene may be involved in different mechanisms of CSC development. Our genetic study provides a basis for understanding the role of CSC susceptibility genes.

Coughing-induced retinal pigment epithelial tear after trabeculectomy combined with pars plana vitrectomy.

Purpose: To report a case of retinal pigment epithelial (RPE) tear after trabeculectomy combined with pars plana vitrectomy (PPV). Observations: A 65-year-old man with neovascular glaucoma due to proliferative diabetic retinopathy presented with visual impairment and elevated intraocular pressure (IOP) in the right eye and underwent trabeculectomy combined with PPV. Three weeks after surgery, the best-corrected visual acuity (logarithm of minimal angle of resolution) improved from 3.0 to 0.30, and the IOP was controlled within normal limits. Four weeks after the surgery, he noticed visual impairment and ocular pain in the right eye after continuous coughing associated with asthma. Fundus examination revealed bullous retinal detachment, choroidal detachment, and submacular hemorrhage (SMH) due to a giant RPE tear at the posterior pole. Visual acuity worsened considerably to 1.7, while IOP was not elevated (6 mmHg). The patient received PPV with recombinant tissue plasminogen activator (rt-PA) and fluid/air exchange for internal tamponade and achieved anatomic retinal and choroidal attachments. Conclusions and importance: The acute increase in hydrostatic pressure in the choroidal interstitium due to continuous coughing induces an RPE tear. Vitrectomy with rt-PA and fluid/air exchange may be a favorable treatment for exudative retinal detachment and SMH due to RPE tears.

Genome-wide Survival Analysis for Macular Neovascularization Development in Central Serous Chorioretinopathy Revealed Shared Genetic Susceptibility with Polypoidal Choroidal Vasculopathy.

PURPOSE: To identify susceptibility genes for macular neovascularization (MNV) development in central serous chorioretinopathy (CSC). DESIGN: Genome-wide survival analysis using a longitudinal cohort study. PARTICIPANTS: We included 402 and 137 patients with CSC but without MNV at their first visit from the Kyoto CSC Cohort and Kobe CSC dataset, respectively. All patients underwent detailed ophthalmic examinations, including multimodal imaging, such as fundus autofluorescence, spectral-domain OCT, and fluorescein angiography/indocyanine green angiography or OCT angiography. METHODS: We conducted a genome-wide survival analysis using the Kyoto CSC Cohort. We applied the Cox proportional hazard model to adjust for age, sex, and the first principal component. Single nucleotide polymorphisms (SNPs) with P values < 1.0 × 10-5 were carried forward to the replication in the Kobe CSC dataset. Moreover, we evaluated the contribution of previously reported age-related macular degeneration (AMD) susceptibility loci. We used FUMA and ToppFun for the functional enrichment analysis. MAIN OUTCOME MEASURES: The association between SNPs and MNV development in patients with CSC. RESULTS: Rs370974631 near ARMS2 displayed a genome-wide significant association in the meta-analysis of discovery and replication result (hazard ratio [HR]meta, 3.63; Pmeta = 5.76 × 10-9). Among previously reported AMD susceptibility loci, we additionally identified CFH rs800292 (HR, 0.39, P = 2.55 × 10-4), COL4A3 rs4276018 (HR, 0.26, P = 1.56 × 10-3), and B3GALTL rs9564692 (HR, 0.56, P = 8.30 × 10-3) as susceptibility loci for MNV development in CSC. The functional enrichment analysis revealed significant enrichment of 8 pathways (GO:0051561, GO:0036444, GO:0008282, GO:1990246, GO:0015272, GO:0030955, GO:0031420, and GO:0005242) related to ion transport. CONCLUSIONS: ARMS2, CFH, COL4A3, and B3GALTL were identified as susceptibility genes for MNV development in CSC. These 4 genes are known as susceptibility genes for AMD, whereas COL4A3 and B3GALTL were previously reported to be polypoidal choroidal vasculopathy (PCV)-specific susceptibility genes. Our findings revealed the shared genetic susceptibility between PCV and MNV secondary to CSC.

Distribution of Choroidal Thickness and Choroidal Vessel Dilation in Healthy Japanese Individuals: The Nagahama Study.

Purpose: To report fundamental epidemiologic data for choroidal parameters such as choroidal thickness and index of choroidal vascularity in Japanese individuals and to evaluate their correlations with age, sex, systemic parameters, and other ocular parameters. Design: Population-based cohort study. Participants: A total of 9850 individuals participated in the first follow-up of the Nagahama Prospective Cohort for Comprehensive Human Bioscience (the Nagahama Study) conducted between 2013 and 2016. Methods: All participants underwent standardized ophthalmic examinations, including OCT with enhanced depth imaging (EDI; RS-3000 Advance; Nidek). We manually segmented the choroidoscleral interface to measure subfoveal choroidal thickness (SFCT) and calculated the normalized choroidal intensity obtained with EDI (NCIEDI) and choroidal vascularity index (CVI). These are indices of choroidal brightness in OCT and reportedly represent the dilation of choroidal vessels. After summarizing the age-sex stratified distributions of SFCT, NCIEDI, and CVI, their associations with age, sex, axial length (AL), and spherical equivalent (SE) were evaluated using linear regression analysis with adjustments for possible confounders. Main Outcome Measures: Distribution of SFCT, NCIEDI, and CVI in the healthy Japanese population and their characteristics. Results: Age-sex standardized SFCT, NCIEDI, and CVI were 291.2 µm, 0.653, and 66.88%, respectively. In both men and women, SFCT was associated negatively with age (P < 0.001) and NCIEDI was associated positively with age (P < 0.001). Although both SFCT and NCIEDI did not differ significantly between men and women overall (P = 0.87 and P = 0.21, respectively), among younger participants (35-50 years of age), men showed significantly greater SFCT than women (P < 0.001). Only in men was CVI associated positively with age (P < 0.001). In the multivariable analysis, SFCT was associated significantly with age, sex, AL, SE, and the interaction term of age and sex (P < 0.001). Independent of SFCT, NCIEDI and CVI were associated significantly with age (P < 0.001). Conclusions: We report normative Japanese SFCT, NCIEDI, and CVI data using a large general Japanese cohort. The association analysis of SFCT with NCIEDI and CVI suggested that younger individuals have a more lumen-rich choroid for their choroidal thickness than older individuals.

Deep phenotype unsupervised machine learning revealed the significance of pachychoroid features in etiology and visual prognosis of age-related macular degeneration.

Unsupervised machine learning has received increased attention in clinical research because it allows researchers to identify novel and objective viewpoints for diseases with complex clinical characteristics. In this study, we applied a deep phenotyping method to classify Japanese patients with age-related macular degeneration (AMD), the leading cause of blindness in developed countries, showing high phenotypic heterogeneity. By applying unsupervised deep phenotype clustering, patients with AMD were classified into two groups. One of the groups had typical AMD features, whereas the other one showed the pachychoroid-related features that were recently identified as a potentially important factor in AMD pathogenesis. Based on these results, a scoring system for classification was established; a higher score was significantly associated with a rapid improvement in visual acuity after specific treatment. This needs to be validated in other datasets in the future. In conclusion, the current study demonstrates the usefulness of unsupervised classification and provides important knowledge for future AMD studies.

Characteristics of Pachychoroid Diseases and Age-Related Macular Degeneration: Multimodal Imaging and Genetic Backgrounds.

The emergence of pachychoroid disease is changing the concept of age-related macular degeneration (AMD). The concept of pachychoroid diseases was developed through clinical observation of multimodal images of eyes with AMD and central serous chorioretinopathy; however, recent genetic studies have provided a proof of concept for pachychoroid spectrum disease, which should be differentiated from drusen-driven AMD. The genetic confirmation of pachychoroid concept further provides novel viewpoints to decode previously reported findings, which facilitates an understanding of the true nature of pachychoroid diseases and AMD. The purpose of this review was to elucidate the relationship between pachychoroid diseases and AMD by interpreting previous findings on pachychoroid diseases and AMD from the novel viewpoints of genetic associations. We confirmed that previous genetic studies supported the concept of pachychoroid diseases. From a genetic viewpoint, the presence of thick choroid and the presence of choroidal vascular hyperpermeability were important characteristics of pachychoroid spectrum diseases. Previous studies have also suggested the classification of polypoidal choroidal vasculopathy (PCV) into two subtypes, pachychoroid neovasculopathy and drusen-driven PCV. Genetic viewpoints will be beneficial to rearrange subtypes of drusen-driven AMD and pachychoroid spectrum diseases. Further genetic studies are needed to investigate pachyvessels, pachydrusen and the significance of polypoidal lesions in pachychoroid neovasculopathy and drusen-driven AMD/PCV.

Genetic biomarkers in the VEGF pathway predicting response to anti-VEGF therapy in age-related macular degeneration.

OBJECTIVE: Age-related macular degeneration (ARMD) is a leading cause of visual impairment. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard treatment for wet ARMD. There is however, variability in patient responses, suggesting patient-specific factors influencing drug efficacy. We tested whether single nucleotide polymorphisms (SNPs) in genes encoding VEGF pathway members contribute to therapy response. METHODS AND ANALYSIS: A retrospective cohort of 281 European wet ARMD patients treated with anti-VEGF was genotyped for 138 tagging SNPs in the VEGF pathway. Per patient, we collected best corrected visual acuity at baseline, after three loading injections and at 12 months. We also registered the injection number and changes in retinal morphology after three loading injections (central foveal thickness (CFT), intraretinal cysts and serous neuroepithelium detachment). Changes in CFT after 3 months were our primary outcome measure. Association of SNPs to response was assessed by binomial logistic regression. Replication was attempted by associating visual acuity changes to genotypes in an independent Japanese cohort. RESULTS: Association with treatment response was detected for seven SNPs, including in FLT4 (rs55667289: OR=0.746, 95% CI 0.63 to 0.88, p=0.0005) and KDR (rs7691507: OR=1.056, 95% CI 1.02 to 1.10, p=0.005; and rs2305945: OR=0.963, 95% CI 0.93 to 1.00, p=0.0472). Only association with rs55667289 in FLT4 survived multiple testing correction. This SNP was unavailable for testing in the replication cohort. Of six SNPs tested for replication, one was significant although not after multiple testing correction. CONCLUSION: Identifying genetic variants that define treatment response can help to develop individualised therapeutic approaches for wet ARMD patients and may point towards new targets in non-responders.

Outcome of primary vitrectomy in phakic patients aged younger than 50 years with rhegmatogenous retinal detachments.

PURPOSE: To evaluate the visual outcome, primary anatomic success, and cataract progression of phakic eyes of patients aged younger than 50 years treated for rhegmatogenous retinal detachment (RRD) with primary pars plana vitrectomy (PPV). METHODS: This was a retrospective, observational, cross-sectional study. The data from 53 RRD patients undergoing PPV were analyzed. The time course changes in best-corrected visual acuity (BCVA) and cataract formation were examined. RESULTS: The 53 patients had a mean age of 37.8 years. Forty-eight eyes (90.6 %) achieved anatomic success after the primary surgery. The BCVA improved significantly after surgery (mean ± SD -0.091 ± 0.146) when compared with the baseline (mean ± SD 0.214 ± 0.597; P = 0.0001). No patient aged younger than 40 years (mean 32.5 years; range 17-39) developed significant lens opacity or received cataract surgery within the first 3 years. Of the patients aged older than 40 years (mean 43.8 years; range 40-49), 22 % developed significant lens opacity and received cataract surgery within the first 3 years. A significant difference was found in cataract progression between the two groups within the first 3 years (P = 0.0217), but not over the entire follow-up period (P = 0.1679). CONCLUSIONS: We found that lens-sparing PPV for RRD in patients aged younger than 50 years had a reasonable success rate, although cataract progression was evident during the follow-up period in patients aged older than 40 years.

A comparison of patient pain and visual outcome using topical anesthesia versus regional anesthesia during cataract surgery.

PURPOSE: The purpose of this study was to compare the level of patient pain during the phacoemulsification and implantation of foldable intraocular lenses while under topical, intracameral, or sub-Tenon lidocaine. PATIENTS AND METHODS: This was a retrospective study. Three hundred and one eyes subjected to cataract surgery were included in this study. All eyes underwent phacoemulsification surgery and intraocular lens implantation using topical, sub-Tenon, or intracameral anesthesia. The topical group received 4% lidocaine drops, and the intracameral group received a 0.1-0.2 cc infusion of 1% preservative-free lidocaine into the anterior chamber through the side port combined with topical drops of lidocaine. The sub-Tenon group received 2% lidocaine. Best-corrected visual acuity, corneal endothelial cell loss, and intraoperative pain level were evaluated. Pain level was assessed on a visual analog scale (range 0-2). RESULTS: There were no significant differences in visual outcome and corneal endothelial cell loss between the three groups. The mean pain score in the sub-Tenon group was significantly lower than that in the topical and intracameral groups (P=0.0009 and P=0.0055, respectively). In 250 eyes without high myopia (< -6D), there were no significant differences in mean pain score between the sub-Tenon and intracameral groups (P=0.1417). No additional anesthesia was required in all groups. CONCLUSION: Intracameral lidocaine provides sufficient pain suppressive effects in eyes without high myopia, while sub-Tenon anesthesia is better for cataract surgery in eyes with high myopia.

Foveal Photoreceptor Deformation as a Significant Predictor of Postoperative Visual Outcome in Idiopathic Epiretinal Membrane Surgery.

PURPOSE: The purpose of this study was to determine whether the outer nuclear layer (ONL) deformation detected by spectral-domain optical coherence tomography (SD-OCT) is correlated with visual acuity before and after surgery in patients with idiopathic epiretinal membrane (ERM). METHODS: Forty-four eyes of 44 patients who underwent vitreous surgery for treatment of ERM were included. All patients underwent comprehensive ophthalmologic evaluations including measurement of best corrected visual acuity (BCVA) and SD-OCT before and after surgery. The central foveal thickness (CFT), foveal ONL thickness, juxtafoveal ONL plus outer plexiform layer (OPL) thickness, photoreceptor outer segment thickness, and size of the disrupted interdigitation zone (IZ) line were measured. We defined the "photoreceptor deformation index" (PDI) as the ratio of foveal ONL thickness to the juxtafoveal ONL plus OPL thickness. RESULTS: Multiple regression analysis showed that the only significant predictor of preoperative mean logarithm of the minimum angle of resolution (logMAR) BCVA was preoperative CFT (P < 0.0001). Preoperative PDI (P < 0.0001) and disrupted IZ diameter (P = 0.0242) were positively correlated with logMAR at 3 months after surgery. PDI (P < 0.0001) and disrupted IZ diameter (P = 0.0351) were also positively correlated with logMAR BCVA at 6 months after surgery. The only significant predictor of logMAR at 12 months after surgery was preoperative PDI (P < 0.0001). CONCLUSIONS: Preoperative PDI was most significantly correlated with postoperative BCVA. These results suggest that PDI is a novel parameter predicting visual outcome after surgery in eyes with ERM.

Two cases of malignant glaucoma unresolved by pars plana vitrectomy.

Malignant glaucoma, which is characterized by a shallow or flat anterior chamber with high intraocular pressure, can usually be resolved by pars plana vitrectomy with anterior hyaloidectomy. We describe two cases in which malignant glaucoma was refractory to conventional treatment and complete vitrectomy. Case one an 88-year-old woman with pseudoexfoliation glaucoma underwent trabeculotomy and subsequently developed malignant glaucoma. Four months after transient recovery by pars plana vitrectomy, the malignant glaucoma recurred. She underwent peripheral iridectomy and local zonulectomy with successful control of her intraocular pressure. In case two, an 85-year-old man had a history of pseudoexfoliation glaucoma. Seven months after phacoemulsification and intraocular lens implantation, he developed malignant glaucoma that was refractory to pars plana vitrectomy. He underwent peripheral iridectomy, goniosynechialysis and trabectome surgery resulting in the successful control of his intraocular pressure. In rare cases of malignant glaucoma refractive to vitrectomy, peripheral iridectomy with or without local zonulectomy is a reasonable and minimally invasive surgical procedure.