Comparative risk of blindness and vision-threatening ocular comorbidities in patients with Behçet's disease versus the general population.

OBJECTIVE: To compare the risk of blindness and vision-threatening ocular comorbidities in patients with Behçet's disease (BD) vs the general population. METHODS: Using 2002-2017 Korea National Health Insurance Service database, we did a population-based cohort study comparing newly diagnosed BD patients and age- and sex-matched non-BD controls at a 1:5 ratio. The primary outcome was blindness, defined as a best-corrected visual acuity of ≤20/500 in the better-seeing eye. Secondary outcomes were vision-threatening ocular comorbidities (cataract, glaucoma and retinal disorders) that require surgical interventions and incident uveitis. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. We performed subgroup analyses by sex and BD diagnosis age. RESULTS: We included 31 228 BD patients and 156 140 controls. During a follow-up of 9.39 years, the incidence rate of blindness per 1000 person-years was 0.24 in BD and 0.02 in controls with an HR of 10.73 (95% CI 7.10, 16.22). The HR for secondary outcomes was 2.06 (95% CI 1.98, 2.15) for cataract surgery, 5.43 (4.57, 6.45) for glaucoma surgery and 2.71 (2.39, 3.07) for retinal surgery. The HR of incident uveitis was 6.19 (95% CI 5.83, 6.58). Males suffered a disproportionately higher risk of blindness than females due to greater severity rather than a lower incidence of uveitis. The risk of uveitis and blindness decreased as BD diagnosis age increased. CONCLUSIONS: In this large population-based cohort study, BD patients compared with the general population have a 10.73-fold risk of blindness in 10 years and also a substantially higher risk of diverse ocular comorbidities that pose potential threats to vision.

Sequential structural and functional change in geographic atrophy on multimodal imaging in non-exudative age-related macular degeneration.

PURPOSE: To investigate the temporal order of photoreceptor atrophy, retinal pigment epithelium (RPE) atrophy and visual acuity loss in patients with center-involving geographic atrophy (GA) in non-exudative age-related macular degeneration (neAMD). METHODS: Forty eyes of 25 consecutive patients who eventually developed center-involving GA were investigated. Fundus autofluorescence (FAF) and infrared image coupled optical coherence tomography (OCT) were acquired at each visit. Development of RPE atrophy and photoreceptor atrophy was defined as abnormal hyper/hypo-fluorescence on FAF and photoreceptor loss on OCT over 50% of the vertical or horizontal diameters of the center 1 mm circle, respectively. Visual acuity loss was defined as worsening of more than 0.2 logMAR compared to baseline. Kaplan-Meier analyses was performed to compare the sequential order of these three events. RESULTS: Mean age was 72.72 ± 8.63 years, and follow-up duration was 27.36 ± 17.22 months, with an average number of visits of 3.04 ± 1.54 during follow-up. GA progressed from photoreceptor atrophy on OCT, RPE atrophy on FAF, and then to vision loss (p < 0.001). The median survival time of photoreceptors preceded that of visual acuity by 16.3 months, and the median survival time of RPE preceded that of visual acuity by 7.0 months. At baseline, majority of eyes showed drusen only (57.5%), while the most common feature was incomplete RPE and outer retinal atrophy at 3-year follow-up (40.4%). CONCLUSION: In the progression of center-involving GA, photoreceptor atrophy on OCT and RPE atrophy on FAF precedes visual decline, and can act as biomarkers predicting future visual decline within the following years.

Evaluation of changes for sebum, skin pore, texture, and redness before and after sleep in oily and nonoily skin.

BACKGROUND: People whose skin type is oily have experienced an esthetic and hygienic discomfort due to the excessive secretion of the sebum during the day and night time, and therefore sebum control is required. In this study, we aimed to find out whether the skin status between the oily and nonoily skin indicates a significant difference before and after sleep. MATERIALS AND METHODS: Forty Korean males and females whose skin type was oily or nonoily participated in this study. To investigate the difference of the skin between oily and nonoily skin before and after sleep, we measured the sebum, skin pore, texture, and redness on their cheek at baseline and after 4-h sleep. Moreover, the significant level was determined at p < 0.05. RESULTS: Parameters of sebum and skin pore significantly increased after 4-h sleep compared with baseline in the oily and nonoily skin (p < 0.05). Moreover, the increment of sebum and pore parameters in the oily skin was significantly higher than those in the nonoily skin (p < 0.05). In the case of skin texture and redness, parameters of them were significantly changed after 4-h sleep compared with baseline only in the oily skin (p < 0.05), and there was no significant difference among groups. CONCLUSIONS: We found that the change rates of the sebum secretion and skin pore in oily skin were significantly higher than those in nonoily skin after 4-h sleep. These results suggest the necessity of the skin care depending on the skin type before sleeping.

Microbial diagnosis of endophthalmitis using nanopore amplicon sequencing.

OBJECTIVES: We investigated whether nanopore amplicon sequencing of aqueous humor was capable of rapid pathogen identification in infectious endophthalmitis. METHODS: 5 cases of culture-positive bacterial endophthalmitis and 3 cases of fungal endophthalmitis (1 culture-positive and 2 presumed) were included. DNA was extracted from the aqueous humor and vitreous specimen, and PCR of bacterial rDNA (16S) and fungal rDNA (ITS1 and D1/2/3) was performed. Then, nanopore amplicon sequencing was performed for 2 h. The results of amplicon sequencing were compared to those of conventional culture studies. RESULTS: In all cases, pathogens were identified by amplicon sequencing of aqueous humor specimens. In 3 cases of bacterial endophthalmitis, the identified microbes were confirmed by culture studies of both aqueous humor and vitreous specimens. In 2 cases of bacterial and 1 case of fungal endophthalmitis, the identified pathogens were confirmed only by culture studies of vitreous specimens. In all cases, amplicon sequencing identified pathogen in a shorter turnaround time than culture studies. In 2 cases with negative culture results, amplicon sequencing of aqueous humor identified fungal pathogens. CONCLUSIONS: Our data demonstrates the potential of amplicon nanopore sequencing using aqueous humor to enable rapid, sensitive and less invasive microbial diagnosis of endophthalmitis.

Embryonic stem cell-derived photoreceptor precursor cells differentiated by coculture with RPE cells.

Purpose: To describe the derivation of photoreceptor precursor cells from human embryonic stem cells by coculture with RPE cells. Methods: Human embryonic stem cells were induced to differentiate into neural precursor cells and then cocultured with RPE cells to obtain cells showing retinal photoreceptor features. Immunofluorescent staining, reverse transcription-PCR (RT-PCR), and microarray analysis were performed to identify photoreceptor markers, and a cGMP assay was used for in vitro functional analysis. After subretinal injection in rat animal models, retinal function was determined with electroretinography and optokinetic response detection, and immunofluorescent staining was performed to assess the survival of the injected cells. Results: Cocultured cells were positive for rhodopsin, red and blue opsin, recoverin, and phosphodiesterase 6 beta on immunofluorescent staining and RT-PCR. Serial detection of stem cell-, neural precursor-, and photoreceptor-specific markers was noted in each stage of differentiation with microarray analysis. Increased cGMP hydrolysis in light-exposed conditions compared to that in dark conditions was observed. After the subretinal injection in the rats, preservation of optokinetic responses was noted up to 20 weeks, while electroretinographic response decreased. Survival of the injected cells was confirmed with positive immunofluorescence staining of human markers at 8 weeks. Conclusions: Cells showed photoreceptor-specific features when stem cell-derived neurogenic precursors were cocultured with RPE cells.

Explaining the Rationale of Deep Learning Glaucoma Decisions with Adversarial Examples.

PURPOSE: To illustrate what is inside the so-called black box of deep learning models (DLMs) so that clinicians can have greater confidence in the conclusions of artificial intelligence by evaluating adversarial explanation on its ability to explain the rationale of DLM decisions for glaucoma and glaucoma-related findings. Adversarial explanation generates adversarial examples (AEs), or images that have been changed to gain or lose pathologic characteristic-specific traits, to explain the DLM's rationale. DESIGN: Evaluation of explanation methods for DLMs. PARTICIPANTS: Health screening participants (n = 1653) at the Seoul National University Hospital Health Promotion Center, Seoul, Republic of Korea. METHODS: We trained DLMs for referable glaucoma (RG), increased cup-to-disc ratio (ICDR), disc rim narrowing (DRN), and retinal nerve fiber layer defect (RNFLD) using 6430 retinal fundus images. Surveys consisting of explanations using AE and gradient-weighted class activation mapping (GradCAM), a conventional heatmap-based explanation method, were generated for 400 pathologic and healthy patient eyes. For each method, board-trained glaucoma specialists rated location explainability, the ability to pinpoint decision-relevant areas in the image, and rationale explainability, the ability to inform the user on the model's reasoning for the decision based on pathologic features. Scores were compared by paired Wilcoxon signed-rank test. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUC), sensitivities, and specificities of DLMs; visualization of clinical pathologic changes of AEs; and survey scores for locational and rationale explainability. RESULTS: The AUCs were 0.90, 0.99, 0.95, and 0.79 and sensitivities were 0.79, 1.00, 0.82, and 0.55 at 0.90 specificity for RG, ICDR, DRN, and RNFLD DLMs, respectively. Generated AEs showed valid clinical feature changes, and survey results for location explainability were 3.94 ± 1.33 and 2.55 ± 1.24 using AEs and GradCAMs, respectively, of a possible maximum score of 5 points. The scores for rationale explainability were 3.97 ± 1.31 and 2.10 ± 1.25 for AEs and GradCAM, respectively. Adversarial example provided significantly better explainability than GradCAM. CONCLUSIONS: Adversarial explanation increased the explainability over GradCAM, a conventional heatmap-based explanation method. Adversarial explanation may help medical professionals understand more clearly the rationale of DLMs when using them for clinical decisions.

Development and Validation of Deep Learning Models for Screening Multiple Abnormal Findings in Retinal Fundus Images.

PURPOSE: To develop and evaluate deep learning models that screen multiple abnormal findings in retinal fundus images. DESIGN: Cross-sectional study. PARTICIPANTS: For the development and testing of deep learning models, 309 786 readings from 103 262 images were used. Two additional external datasets (the Indian Diabetic Retinopathy Image Dataset and e-ophtha) were used for testing. A third external dataset (Messidor) was used for comparison of the models with human experts. METHODS: Macula-centered retinal fundus images from the Seoul National University Bundang Hospital Retina Image Archive, obtained at the health screening center and ophthalmology outpatient clinic at Seoul National University Bundang Hospital, were assessed for 12 major findings (hemorrhage, hard exudate, cotton-wool patch, drusen, membrane, macular hole, myelinated nerve fiber, chorioretinal atrophy or scar, any vascular abnormality, retinal nerve fiber layer defect, glaucomatous disc change, and nonglaucomatous disc change) with their regional information using deep learning algorithms. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve and sensitivity and specificity of the deep learning algorithms at the highest harmonic mean were evaluated and compared with the performance of retina specialists, and visualization of the lesions was qualitatively analyzed. RESULTS: Areas under the receiver operating characteristic curves for all findings were high at 96.2% to 99.9% when tested in the in-house dataset. Lesion heatmaps highlight salient regions effectively in various findings. Areas under the receiver operating characteristic curves for diabetic retinopathy-related findings tested in the Indian Diabetic Retinopathy Image Dataset and e-ophtha dataset were 94.7% to 98.0%. The model demonstrated a performance that rivaled that of human experts, especially in the detection of hemorrhage, hard exudate, membrane, macular hole, myelinated nerve fiber, and glaucomatous disc change. CONCLUSIONS: Our deep learning algorithms with region guidance showed reliable performance for detection of multiple findings in macula-centered retinal fundus images. These interpretable, as well as reliable, classification outputs open the possibility for clinical use as an automated screening system for retinal fundus images.

Retina thickness as a marker of neurodegeneration in prodromal lewy body disease.

OBJECTIVES: We investigated retinal change and its relationship with neurodegeneration markers in a prodromal Parkinson cohort. METHODS: A total of 30 patients with idiopathic rapid eye movement sleep behavior disorder were recruited. Participants underwent olfactory testing, macular optical coherence tomography, microperimetry, contrast sensitivity test, and brain N-(3-[18 F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane positron emission tomography. We measured the ganglion cell complex thicknesses and investigated its correlation with olfactory function and striatal dopamine transporter availability. A linear mixed-effect model was applied with adjustment for multiple comparisons. RESULTS: The parafoveal ganglion-cell-complex thickness in this cohort lay between our healthy control and drug-naïve Parkinson's disease group data. Idiopathic rapid eye movement sleep behavior disorder patients also had contrast sensitivity impairment as in Parkinson's disease with a nonsignificant change in macular sensitivities. Macular ganglion cell complex thickness correlated with olfactory scores and with striatal dopamine transporter availabilities. CONCLUSIONS: Macular ganglion cell complex thinning may be a marker of neurodegeneration in prodromal Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society.

Contrast sensitivity impairment in drug-naïve Parkinson's disease patients associates with early cognitive decline.

OBJECTIVES: To investigate the contrast sensitivity function in drug-naïve Parkinson's disease (PD) patients and its predictive value with longitudinal follow-up data. METHODS: We included newly diagnosed non-demented PD patients who performed contrast sensitivity test between 2013 and 2014. Contrast sensitivity function at drug-naïve state in PD patients was compared with age-matched normal control data of our center. Correlation between contrast sensitivity function and parkinsonian motor and non-motor features including the Mini-Mental State Exam (MMSE) score at the time of diagnosis were analyzed by linear regression. With longitudinal follow-up data after initiating anti-parkinsonian therapy, the risk conferred on subsequent visual hallucinations and cognitive impairment requiring anti-dementia drugs was analyzed by dichotomizing PD group based on the initial contrast sensitivity function. RESULTS: Forty-eight patients were finally included, and mean follow-up periods were 43 months. Contrast sensitivity function in drug-naïve PD patients was significantly worse than controls. Contrast sensitivity function correlated with sleep disturbance (p = 0.001) and global cognitive status reflected by the MMSE score (p = 0.020). It also associated with further decline in the MMSE during the follow-ups (p = 0.029). Patients with below average contrast sensitivity function at the time of diagnosis showed higher risk of cognitive decline requiring anti-dementia drugs (adjusted odds ratio = 4.68, p = 0.04) and of visual hallucinations (adjusted odds ratio = 12.54, p = 0.04) than those above average function during the follow-up. CONCLUSION: Contrast sensitivity impairment in drug-naïve PD patients associates with clinical demand for therapeutic intervention of cognitive decline as well as development of visual hallucinations in the early course of the disease.

A Novel Fundus Image Reading Tool for Efficient Generation of a Multi-dimensional Categorical Image Database for Machine Learning Algorithm Training.

BACKGROUND: We described a novel multi-step retinal fundus image reading system for providing high-quality large data for machine learning algorithms, and assessed the grader variability in the large-scale dataset generated with this system. METHODS: A 5-step retinal fundus image reading tool was developed that rates image quality, presence of abnormality, findings with location information, diagnoses, and clinical significance. Each image was evaluated by 3 different graders. Agreements among graders for each decision were evaluated. RESULTS: The 234,242 readings of 79,458 images were collected from 55 licensed ophthalmologists during 6 months. The 34,364 images were graded as abnormal by at-least one rater. Of these, all three raters agreed in 46.6% in abnormality, while 69.9% of the images were rated as abnormal by two or more raters. Agreement rate of at-least two raters on a certain finding was 26.7%-65.2%, and complete agreement rate of all-three raters was 5.7%-43.3%. As for diagnoses, agreement of at-least two raters was 35.6%-65.6%, and complete agreement rate was 11.0%-40.0%. Agreement of findings and diagnoses were higher when restricted to images with prior complete agreement on abnormality. Retinal/glaucoma specialists showed higher agreements on findings and diagnoses of their corresponding subspecialties. CONCLUSION: This novel reading tool for retinal fundus images generated a large-scale dataset with high level of information, which can be utilized in future development of machine learning-based algorithms for automated identification of abnormal conditions and clinical decision supporting system. These results emphasize the importance of addressing grader variability in algorithm developments.

Investigation of precursor lesions of polypoidal choroidal vasculopathy using contralateral eye findings.

PURPOSE: The purpose was to investigate precursor lesions of polypoidal choroidal vasculopathy (PCV). METHODS: This cross-sectional study involved 276 unaffected contralateral eyes from unilateral PCV patients (Group 1), unilateral typical exudative age-related macular degeneration (AMD) patients (Group 2), and unilateral epiretinal membrane patients (Group 3) as age-matched controls. Grayish-yellow sub-retinal or sub-retinal-pigment-epithelial deposits larger than 63 µm in size with irregular but discrete margins were defined as drusen-like deposits (DLDs). The frequencies of DLDs, drusen, and pigmentary changes in each group were compared. RESULTS: DLDs larger than 125 µm in size were found more frequently in Group 1 (19.5 %) than in Groups 2 (3.4 %) and 3 (3.2 %) (p < 0.001). Soft drusen were discovered more frequently in Group 2 eyes than in Groups 1 and 3 (p < 0.001). Pigmentary changes were found more frequently in Groups 1 and 2 compared to Group 3. Compared with the other groups, Group 1 manifested a higher frequency of choroidal vascular hyperpermeability (p < 0.005) and thicker choroid (p < 0.001). CONCLUSIONS: The precursor lesions of PCV are different from those of exudative AMD. DLDs larger than 125 µm and pigmentary changes may be early preclinical markers of PCV. Long-term longitudinal studies are warranted for validation.

Association of ARMS2 genotype with response to anti-vascular endothelial growth factor treatment in polypoidal choroidal vasculopathy.

BACKGROUND: To investigate whether genetic risk variants for age-related macular degeneration (AMD) are associated with response to intravitreal anti-vascular endothelial growth factor (VEGF) in polypoidal choroidal vasculopathy (PCV) patients. METHODS: This prospective cohort study included 95 treatment-naïve patients that underwent anti-VEGF treatment for PCV for 12 months. Patients were genotyped for 10 single nucleotide polymorphisms in eight AMD-relevant genes. Genotypic association with visual and anatomic outcome measures at 12 months after initial treatment, including mean change in best-corrected visual acuity (BCVA) and total foveal thickness, visual gain of ≥ 15 letters, dry status on optical coherence tomography (OCT), pigment epithelial detachment (PED) regression on OCT, polyp regression on indocyanine green angiography, and injection numbers, were investigated using regression models with adjustment for non-genetic covariates under additive genetic model. RESULTS: In 81 patients who completed 12-month anti-VEGF monotherapy without photodynamic therapy, significant pharmacogenetic association was found between ARMS2 rs10490924 and PED regression on OCT. Proportions of PED regression were 26.4% for TT, 45.7% for TG, and 63.6% for GG genotype, showing additive effect of G allele for higher chance of PED regression (OR, 2.96; 95% CI, 1.38-6.36; corrected P = 0.043). For entire 95 patients, no significant association was found between candidate polymorphisms and receiving photodynamic therapy within 12 months. CONCLUSIONS: In PCV patients, ARMS2 rs10490924 showed association with anatomic therapeutic response to anti-VEGF, suggesting pharmacogenetic relationship.

Complications of Pathologic Myopia.

Pathologic myopia (PM) is one of the leading causes of visual impairment worldwide. The pathophysiology of PM is not fully understood, but the axial elongation of the eye followed by chorioretinal thinning is suggested as a key mechanism. Pathologic myopia may lead to many complications such as chorioretinal atrophy, foveoschisis, choroidal neovascularization, rhegmatogenous retinal detachment, cataract, and glaucoma. Some complications affect visual acuity significantly, showing poor visual prognosis. This article aims to review the types, pathophysiology, treatment, and visual outcome of the complications of PM.

The diagnostic application of targeted re-sequencing in Korean patients with retinitis pigmentosa.

BACKGROUND: Identification of the causative genes of retinitis pigmentosa (RP) is important for the clinical care of patients with RP. However, a comprehensive genetic study has not been performed in Korean RP patients. Moreover, the genetic heterogeneity found in sensorineural genetic disorders makes identification of pathogenic mutations challenging. Therefore, high throughput genetic testing using massively parallel sequencing is needed. RESULTS: Sixty-two Korean patients with nonsyndromic RP (46 patients from 18 families and 16 simplex cases) who consented to molecular genetic testing were recruited in this study and targeted exome sequencing was applied on 53 RP-related genes. Causal variants were characterised by selecting exonic and splicing variants, selecting variants with low allele frequency (below 1 %), and discarding the remaining variants with quality below 20. The variants were additionally confirmed by an inheritance pattern and cosegregation test of the families, and the rest of the variants were prioritised using in-silico prediction tools. Finally, causal variants were detected from 10 of 18 familial cases (55.5 %) and 7 of 16 simplex cases (43.7 %) in total. Novel variants were detected in 13 of 20 (65 %) candidate variants. Compound heterozygous variants were found in four of 7 simplex cases. CONCLUSION: Panel-based targeted re-sequencing can be used as an effective molecular diagnostic tool for RP.

Pharmacogenetic associations with long-term response to anti-vascular endothelial growth factor treatment in neovascular AMD patients.

PURPOSE: To investigate the pharmacogenetic associations between the genetic risk variants of age-related macular degeneration (AMD) and long-term outcome after intravitreal anti-vascular endothelial growth factor (VEGF) treatment in Korean neovascular AMD patients. METHODS: This prospective study included 394 treatment-naïve patients (394 eyes) that underwent intravitreal anti-VEGF treatment for neovascular AMD for at least 12 months. Patients were genotyped for 17 single nucleotide polymorphisms within 13 AMD-relevant genes. Initially, patients underwent three monthly injections of intravitreal ranibizumab and were retreated as needed with ranibizumab or bevacizumab. For each candidate polymorphism, genotypic associations with treatment outcome measures at months 12 and 24, including mean change in best-corrected visual acuity (BCVA) from baseline, visual gain of ≥15 letters, mean change in central subfield macular thickness (CSMT) from baseline on spectral domain optical coherence tomography (OCT), presence of fluid on OCT, and mean number of injections, were investigated using logistic or linear regression models with adjustment for non-genetic covariates. RESULTS: At month 24, BCVA improved by 4.5 ± 22.5 letters and CSMT decreased by 69.4 ± 112.6 µm from baseline. Regression analysis with Bonferroni correction showed that the TT genotype for VEGFA rs3025039 was associated with a significantly higher chance of a visual gain of ≥15 letters at month 24 than other genotypes (odds ratio, 4.57; 95% confidence interval, 1.89 - 11.1; corrected p = 0.0434). As for tomographic outcome, the minor allele homozygotes for ARMS2 rs10490924 and HTRA1 rs1100638 (GG genotype for both) were associated with a larger CSMT reduction at month 12 than other genotypes, with borderline significance after Bonferroni correction (118.6 ± 132.7 µm versus 62.7 ± 89.7 µm, corrected p = 0.0656 for rs10490924; 115.7 ± 131.7 µm versus 63.6 ± 89.8 µm, corrected p = 0.0528 for rs11200638). No polymorphism showed a significant association with the number of injections. CONCLUSIONS: In this Korean neovascular AMD cohort, treatment outcome after anti-VEGF was found to differ by the genotypes of VEGFA rs3025039, ARMS2 rs10490924, and HTRA1 rs11200638. Given more evidence of pharmacogenetic associations with the anti-VEGF agent, individualized therapeutic approaches based on genetic background could lead to optimal treatment in neovascular AMD.

Low-fluence photodynamic therapy versus ranibizumab for chronic central serous chorioretinopathy: one-year results of a randomized trial.

PURPOSE: To compare the efficacy and safety between low-fluence photodynamic therapy (PDT) and the intravitreal ranibizumab in the treatment of chronic central serous chorioretinopathy (CSC). DESIGN: Prospective, randomized, single-center, parallel-arm, controlled trial. PARTICIPANTS: Thirty-four eyes of 32 patients with chronic CSC with >6 months' duration of symptoms or recurrent CSC were randomly placed into the low-fluence PDT group (n = 18) or the ranibizumab group (n = 16). INTERVENTION: The patients underwent a single session of low-fluence PDT or 3 consecutive monthly injections of ranibizumab. Rescue treatment was available from month 3 if the subretinal fluid (SRF) persisted or recurred after primary treatment; low-fluence PDT was given to the ranibizumab group and intravitreal ranibizumab to the low-fluence PDT group. MAIN OUTCOME MEASURES: The primary outcome was the proportion of eyes with complete resolution of SRF without rescue treatment. Secondary outcomes included the mean changes in logarithm of the minimum angle of resolution best-corrected visual acuity (BCVA), central retinal thickness (CRT), and angiographic findings from baseline to 12 months. RESULTS: At month 12, 16 eyes (88.9%) of the low-fluence PDT group maintained complete resolution of SRF without rescue treatment versus 2 eyes (12.5%) in the ranibizumab group (P <0.001). Two eyes (11.1%) in the low-fluence PDT group and 11 eyes (68.8%) in the ranibizumab group met the criteria for rescue treatment (P = 0.001). In the low-fluence PDT group, the mean decrease in CRT from baseline was significantly greater than that in the ranibizumab group until month 6 (P <0.05), but the differences became insignificant thereafter. The improvement in BCVA from baseline was superior in the low-fluence PDT group to that in the ranibizumab group, but the differences were not statistically significant except at month 3 (P = 0.025). On indocyanine green angiography, a significantly greater proportion of the low-fluence PDT group (16 eyes; 88.9%) showed a marked reduction in choroidal hyperpermeability after primary treatment than that of the ranibizumab group (0 eyes; P <0.001). No serious adverse events related to the drugs or procedures were observed. CONCLUSIONS: This study represents the overall superiority of low-fluence PDT compared with intravitreal ranibizumab in the treatment of chronic CSC.

Optical coherence tomography-based ranibizumab monotherapy for retinal angiomatous proliferation in Korean patients.

PURPOSE: To evaluate the visual outcome of optical coherence tomography-based ranibizumab monotherapy in Korean patients with retinal angiomatous proliferation and identify prognostic factors of visual outcome. METHODS: A prospective single-arm clinical study of 31 retinal angiomatous proliferation patients who underwent 3 consecutive monthly intravitreal ranibizumab injections was conducted. Additional treatment was given based on optical coherence tomography at monthly follow-ups over 24 months. RESULTS: Best-corrected visual acuity improved from 48.7 ± 19.3 to 56.3 ± 19.1 letters at 24 months (P = 0.010). Total cumulative numbers of injection were 5.5 ± 2.2 and 7.7 ± 3.4 times at 12 and 24 months, respectively. Older age, larger choroidal neovascularization size, and poor initial best-corrected visual acuity were associated with poor visual outcome. Final best-corrected visual acuity was significantly worse with Stage 3 disease (70.4 ± 5.1, 62.3 ± 11.6, 46.2 ± 22.3 letters improved in each stage; P = 0.015). Among factors associated with poor visual outcome, only the stage of retinal angiomatous proliferation remained statistically significant on multiple linear regression analysis (P = 0.006). Although baseline best-corrected visual acuity was similar, Stage 3 patients exhibited limited visual improvement despite anatomical improvement, and more recurrences requiring more injections. CONCLUSION: Retinal angiomatous proliferation may be successfully managed with ranibizumab monotherapy in Korean patients, with the number of treatments required comparable to other forms of neovascular age-related macular degeneration. However, visual improvement was limited in late-stage RAP.

Genetic factors associated with response to intravitreal ranibizumab in Korean patients with neovascular age-related macular degeneration.

PURPOSE: To investigate the association between genetic risk variants for age-related macular degeneration (AMD) and response to intravitreal ranibizumab in Korean patients with neovascular AMD. METHODS: This prospective study included 273 treatment-naive patients (273 eyes) who underwent 5 monthly injections (Months 0, 1, 2, 3, and 4) of intravitreal ranibizumab for neovascular AMD. Patients were genotyped for 23 single-nucleotide polymorphisms within 12 AMD-relevant genes. For each polymorphism, genotypic association with good response at Month 5, predetermined as visual improvement of ≥ 8 Early Treatment Diabetic Retinopathy Study letters from baseline, was investigated with logistic regression analysis adjusted for age, gender, smoking, baseline Early Treatment Diabetic Retinopathy Study letter, central retinal thickness, lesion area, and type of choroidal neovascularization. RESULTS: At Month 5, visual acuity improved by 9.1 ± 17.6 letters from baseline, and 136 patients (49.8%) were classified as good responders. In logistic regression, no tested polymorphism showed statistically significant association with favorable visual outcome at Month 5. When unadjusted for multiple tests, AA genotype for VEGF rs699947 had an increased chance of good response compared with other genotypes (odds ratio, 3.61; 95% confidence interval, 1.42-9.18; P = 0.0071). CONCLUSION: In this Korean neovascular AMD cohort, there was no statistically significant effect of genotype on early visual outcome after ranibizumab treatment.

Chlorogenic acid supplementation improves multifocal electroretinography in patients with retinitis pigmentosa.

To evaluate the effect of chlorogenic acid supplementation in patients with retinitis pigmentosa, we evaluated objective change in visual function with multifocal electroretinography, along with visual acuity, visual field, standard electroretinography, and contrast sensitivity. Eighteen patients diagnosed with retinitis pigmentosa were enrolled in this prospective, non-comparative, single-arm study. Multifocal electroretinography, best-corrected visual acuity in Early Treatment Diabetic Retinopathy Study letters, total point score on visual field examination with Humphrey Field Analyzer II, electroretinography, and contrast sensitivity were measured and repeated after 3 months supplementation with chlorogenic acid. The amplitude of ring 5 was significantly higher on multifocal electroretinography after 3 months of chlorogenic acid supplementation (7.2 ± 9.5 vs 8.3 ± 10.8 nV/deg(2), mean ± standard deviation, P = 0.022). There were no significant changes in the best-corrected visual acuity, total point score on Humphrey Field Analyzer, 30 Hz flicker amplitude on standard electroretinography, or contrast sensitivity. Chlorogenic acid may have a beneficial effect on the peripheral area at the margins of retinal degeneration, and should be considered as an anti-oxidant for the management of retinitis pigmentosa.