Association of Fundus Autofluorescence Abnormalities and Pachydrusen in Central Serous Chorioretinopathy and Polypoidal Choroidal Vasculopathy.

A specific form of drusen, known as pachydrusen, has been demonstrated to be associated with pachychoroid eye diseases, such as central serous chorioretinopathy (CSC) and polypoidal choroidal vasculopathy (PCV). These pachydrusen have been found in up to 50% of eyes with CSC and PCV and may affect the disease progression and treatment response. This study aims to investigate the association between pachydrusen and changes in fundus autofluorescence (FAF) in eyes with CSC and PCV. A total of 65 CSC patients and 32 PCV patients were evaluated. Pachydrusen were detected using both color fundus photography and spectral-domain optical coherence tomography. The relationships between pachydrusen and FAF changes were then investigated. The prevalence of pachydrusen in CSC and PCV eyes was 16.7% and 61.8%, respectively. The mean age of patients with pachydrusen was significantly older than those without pachydrusen (CSC: 56.3 vs. 45.0 years, p < 0.001; PCV: 68.8 vs. 59.5 years, p < 0.001). No significant difference was found in the mean subfoveal choroidal thickness between eyes with or without pachydrusen. Eyes with pachydrusen were significantly associated with more extensive FAF changes in both CSC and PCV (p < 0.001 and p = 0.037, respectively). The study demonstrated that pachydrusen are more prevalent in PCV than CSC. Increasing age and more extensive abnormalities in FAF are associated with the presence of pachydrusen, suggesting that dysfunction of retinal pigment epithelial cells is associated with pachydrusen.

Association between Retinal Thickness Variability and Visual Acuity Outcome during Maintenance Therapy Using Intravitreal Anti-Vascular Endothelial Growth Factor Agents for Neovascular Age-Related Macular Degeneration.

Previous studies based on clinical trial data have demonstrated that greater fluctuations in retinal thickness during the course of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) is associated with poorer visual acuity outcomes. However, it was unclear whether similar findings would be observed in real-world clinical settings. This study aimed to evaluate the association between retinal thickness variability and visual outcomes in eyes receiving anti-VEGF therapy for nAMD using pro re nata treatment regimen. A total of 64 eyes which received intravitreal anti-VEGF therapy (bevacizumab, ranibizumab or aflibercept) for the treatment of nAMD were evaluated. Variability in spectral-domain optical coherence tomography (OCT) central subfield thickness (CST) was calculated from the standard deviation (SD) values of all follow-up visits after three loading doses from month 3 to month 24. Eyes were divided into quartiles based on the OCT CST variability values and the mean best-corrected visual acuity values at 2 years were compared. At baseline, the mean ± SD logMAR visual acuity and CST were 0.59 ± 0.39 and 364 ± 113 µm, respectively. A significant correlation was found between CST variability and visual acuity at 2 years (Spearman's ρ = 0.54, p < 0.0001), indicating that eyes with lower CST variability had better visual acuity at 2 years. Eyes with the least CST variability were associated with the highest mean visual acuity improvement at 2 years (quartile 1: +9.7 letters, quartile 2: +1.1 letters, quartile 3: -2.5 letters, quartile 4: -9.5 letters; p = 0.018). No significant difference in the number of anti-VEGF injections was found between the four CST variability quartile groups (p = 0.21). These findings showed that eyes undergoing anti-VEGF therapy for nAMD with more stable OCT CST variability during the follow-up period were associated with better visual outcomes. Clinicians should consider adopting treatment strategies to reduce CST variability during the treatment course for nAMD.

Improvement in multifocal electroretinography after half-dose verteporfin photodynamic therapy for central serous chorioretinopathy: a randomized placebo-controlled trial.

PURPOSE: To evaluate retinal functional changes by multifocal electroretinography (mfERG) after photodynamic therapy with half-dose verteporfin in patients with acute central serous chorioretinopathy. METHODS: Thirty-four patients with acute central serous chorioretinopathy were randomly assigned to receive photodynamic therapy with half-dose verteporfin (n = 24) or placebo (n = 10). Multifocal electroretinography was performed at baseline and at 12 months, and serial changes in response amplitudes were expressed as amplitude ratios. The mfERG amplitude ratios, best-corrected visual acuity, and optical coherence tomography central foveal thickness were compared between the verteporfin and placebo groups. Correlation analysis between the mfERG response amplitude ratios and the best-corrected visual acuity changes and reduction in optical coherence tomography central foveal thickness were also performed. RESULTS: At 12 months, the mean visual improvement was 1.8 line and 0.1 line for the verteporfin and placebo groups, respectively (P = 0.003). Eyes in the verteporfin group had significantly lower central foveal thickness (P = 0.028) and higher P1 mfERG response ratios for Rings 1 and 2 at 12 months compared with the eyes in the placebo group (P = 0.030 and P = 0.018, respectively). Significant correlations between mfERG N1 and P1 amplitude ratios at the central rings were observed with both changes in best-corrected visual acuity and reductions in optical coherence tomography central foveal thickness (P < 0.05). CONCLUSIONS: Multifocal electroretinography demonstrated higher retinal function at the central macula objectively in central serous chorioretinopathy patients treated with half-dose verteporfin photodynamic therapy. Changes in best-corrected visual acuity and optical coherence tomography central foveal thickness findings also correlated with mfERG responses of the central macula, confirming the usefulness of mfERG as an objective investigation to evaluate the functional changes in central serous chorioretinopathy.

Correlation between functional and anatomical assessments by multifocal electroretinography and optical coherence tomography in central serous chorioretinopathy.

To evaluate the correlation between functional and anatomical assessments with multifocal electroretinography (mfERG) and optical coherence tomography (OCT) in patients with acute central serous chorioretinopathy (CSC). Thirty-four eyes of 34 patients with acute CSC underwent mfERG and OCT examinations. First-order mfERG N1 and P1 response amplitudes and latencies were analyzed.OCT parameters measured included central subretinal fluid (SRF) thickness, central retinal thickness, total central foveal thickness, vertical, and horizontal diameters of SRF, and macular volume. Correlation analyses were performed between best-corrected visual acuity (BCVA), mfERG parameters, and OCT measurements. Correlation analysis showed that logMAR BCVA was significantly correlated with mfERG N1 amplitudes of rings 1 and 2 (P = 0.006), N1 latency of ring 4 (P = 0.012), and P1 latency of ring 1 (P = 0.036). No significant correlation was observed between logMAR BCVA and any of the OCT measurements. For the correlation between mfERG parameters and OCT measurements, mfERG N1 and P1 latencies of the paracentral rings were significantly correlated with the central SRF thickness (P < or = 0.024), diameters of the SRF (P < or = 0.018), and macular volume (P < or = 0.030). MfERG responses but not OCT measurements correlated with logMAR BCVA in patients with acute CSC. The amount of SRF nonetheless correlated with the mfERG N1 and P1 latencies of the paracentral rings, suggesting that impairment in the conduction of electrical responses in the paracentral macula is proportional to the severity of serous macular detachment in CSC. MfERG and OCT can complement each other in the functional and anatomical assessments in CSC.

Compound heterozygosity of two novel truncation mutations in RP1 causing autosomal recessive retinitis pigmentosa.

Purpose. To evaluate the phenotypic effects of two novel frameshift mutations in the RP1 gene in a Chinese pedigree of autosomal recessive retinitis pigmentosa (ARRP). Methods. Family members of a proband with ARRP were screened for RP1, RHO, NR2E3, and NRL mutations by direct sequencing. Detected RP1 mutations were genotyped in 225 control subjects. Since one family member with the RP1 deletion mutation in exon 2 was found to have age-related macular degeneration (AMD) but not RP, exons 2 and 3 of RP1 were screened in 120 patients with exudative AMD. Major AMD-associated SNPs in the HTRA1 and CFH genes were also investigated. Results. Two novel frameshift mutations in RP1, c.5_6delGT and c.4941_4942insT, were identified in the pedigree. They were absent in 225 control subjects. Family members who were compound heterozygous for the nonsense mutations had early-onset and severe RP, whereas those with only one mutation did not have RP. No mutations in RHO, NR2E3, and NRL were identified in the pedigree. Subject I:2 with AMD carried both at-risk genotypes at HTRA1 rs11200638 and CFH rs800292. No mutation in RP1 exons 2 and 3 was identified in 120 AMD patients. Conclusions. This report is the first to associate ARRP with compound heterozygous nonsense mutations in RP1. Identification of the nonsense-mediated mRNA decay (NMD)-sensitive mutation c.5_6delGT provided further genetic evidence that haploinsufficiency of RP1 is not responsible for RP. The authors propose four classes of truncation mutations in the RP1 gene with different effects on the etiology of RP.

Changes in first- and second-order multifocal electroretinography in idiopathic macular hole and their correlations with macular hole diameter and visual acuity.

PURPOSE: To evaluate the first- and second-order multifocal electroretinography (mfERG) responses in patients with idiopathic macular hole, and their correlations with macular hole diameter measured by optical coherence tomography (OCT) and visual acuity. METHODS: Twenty-four eyes of 24 patients with idiopathic macular hole underwent mfERG and OCT examinations. The response amplitudes and implicit times of the first- and second-order mfERG were analyzed and compared with 20 age-similar normal control subjects. Correlation analyses between visual acuity, apical and basal diameters of the macular hole, and the first- and second-order mfERG amplitudes and implicit times were performed. RESULTS: The first-order mfERG N1 and P1 amplitudes in the central two concentric rings were reduced in macular hole eyes compared with controls (p < 0.006). For the second-order mfERG, only the N1 mfERG amplitude was significantly reduced at ring 6 in macular hole eyes compared with controls (p = 0.030). Correlation analysis showed that apical diameter of macular hole was significantly correlated with the first-order N1 amplitude of rings 2 to 5 (p < 0.024), the first-order P1 amplitude of rings 2 to 6 (p < 0.05), as well as the second-order P1 mfERG amplitudes of rings 3 to 6 and N1 amplitudes of rings 3 to 5 (p < 0.05). LogMAR visual acuity showed significant correlation with apical diameter of the macular hole (p = 0.002), and also with the first-order P1 amplitude of ring 2 (p = 0.024). CONCLUSION: In eyes with idiopathic macular hole, reductions in first-order mfERG responses are limited to the central macula, while the second-order mfERG response abnormalities involved more of the peripheral macular region. OCT measurement of apical and not the basal diameter of macular hole correlated with the severity of retinal dysfunction assessed by both mfERG and visual acuity.

Half-dose verteporfin photodynamic therapy for acute central serous chorioretinopathy: one-year results of a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of photodynamic therapy (PDT) with half-dose verteporfin for treating acute central serous chorioretinopathy (CSC). DESIGN: Prospective, double-masked, placebo-controlled, randomized clinical trial. PARTICIPANTS AND CONTROLS: Sixty-three eyes of 63 patients with acute symptomatic CSC of 3 months' duration or less were recruited. Forty-three eyes were randomized to indocyanine green angiography (ICGA)-guided PDT with half-dose (3 mg/m(2)) verteporfin and 21 eyes were randomized to placebo. INTERVENTION: Patients in the verteporfin group received an infusion of half-dose verteporfin over 8 minutes, followed by ICGA-guided PDT 10 minutes from the start of infusion. Laser was applied for 83 seconds covering the choroidal abnormalities observed in ICGA, with a maximum laser spot size of 4500 mum. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of eyes with absence of subretinal fluid at the macula at 12 months. Secondary outcome measures included changes in mean logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), subjective symptoms, optical coherence tomography (OCT) results, central foveal thickness (CFT), and angiographic findings during the 12-month study period. RESULTS: Thirty-nine patients in the verteporfin group and 19 patients in the placebo group completed 12 months of follow-up. Thirty-seven (94.9%) eyes in the verteporfin group compared with 11 (57.9%) eyes in the placebo group showed absence of subretinal fluid at the macula at 12 months (P = 0.001). The mean logMAR BCVA at 12 months was significantly better in the verteporfin group compared with the placebo group: -0.05 and 0.05, respectively (P = 0.008). All 39 (100%) verteporfin-treated eyes had stable or improved vision, compared with 15 (78.9%) eyes in the placebo group (P = 0.009). The mean OCT CFT for the verteporfin group also was significantly lower compared with the placebo group at 12 months (P = 0.001). No ocular or systemic adverse event was encountered in the study. CONCLUSIONS: Photodynamic therapy with half-dose verteporfin is effective in treating acute symptomatic CSC, resulting in a higher proportion of patients with absence of exudative macular detachment and better visual acuity compared with placebo.

The effect of parental history of myopia on children's eye size and growth: results of a longitudinal study.

PURPOSE: To evaluate the effect of parental myopia on eye size and growth in Chinese children. METHODS: A school-based, cross-sectional survey was performed in Chinese children 5 to 16 years of age. A longitudinal cohort study was conducted 1 year later. The effects of parental myopia, parental education level, and near work performed by the child on the refractive error and ocular biometry of the child were assessed. RESULTS: There were 7560 children enrolled in the initial study (response rate: 76.3%). One year later, 4468 children (response rate: 75.9%) in the original cohort (with the exception of those who had completed primary schooling) were evaluated, to determine eye growth. Although children with a stronger parental history of myopia tended to be less hyperopic before the onset of myopia (spherical equivalent refraction [SER] = 0.43 D, 0.67 D, and 0.68 D in children with two, one, and no myopic parents respectively; P = 0.007), the axial lengths did not follow the same pattern (axial length [AL] = 23.11, 23.07, and 23.15 mm; P = 0.429). Eye growth and myopic shift in refraction occurred more rapidly among children with a stronger parental history of myopia (annual AL growth/myopia progression = 0.37 mm/-0.22 D, 0.26 mm/-0.07 D, and 0.20 mm/-0.02 D in children with two, one, and no myopic parents, respectively; P < 0.001). CONCLUSIONS: Ocular biometric data in Chinese children suggest that parental history of myopia influences the growth rate of the eye, rather than its size before the onset of myopia, as previously reported in Caucasian children. Further longitudinal studies involving children of different ethnicities are warranted.

Safety enhanced photodynamic therapy for chronic central serous chorioretinopathy: one-year results of a prospective study.

PURPOSE: To evaluate the efficacy of a safety enhanced photodynamic therapy (PDT) protocol with half-dose verteporfin for treating chronic central serous chorioretinopathy (CSC). METHODS: Forty-eight eyes of 48 patients with symptomatic chronic CSC underwent indocyanine green angiography guided PDT with half dose (3 mg/m) verteporfin. Outcome measures included logMAR best-corrected visual acuity (BCVA), central retinal thickness, and angiographic changes during the 12-month study period. RESULTS: The mean CSC duration was 8.2 months (range, 3-40 months). At 12 months after PDT, the mean logMAR BCVA improved from 0.31 to 0.15 (P < 0.001). The mean improvement was 1.6 lines and 45 (95.8%) eyes had stable or improved vision. Eyes without pigment epithelial detachment (PED) had significantly greater visual improvement compared with eyes with PED (P = 0.031). Patients with CSC of 6 months or less or younger than 45 years were more likely to gain vision by two or more lines after treatment (P = 0.007 and P = 0.018, respectively). Forty (83.3%) eyes had complete resolution of serous detachment at 3 months, with 43 (89.6%) eyes at 12 months. CONCLUSIONS: The safety enhanced PDT protocol appeared to be beneficial for patients with chronic CSC. Further controlled study is warranted to evaluate the safety and efficacy of this treatment option.

First and second-order kernel multifocal electroretinography abnormalities in acute central serous chorioretinopathy.

PURPOSE: To evaluate the first and second-order kernel multifocal electroretinogram (mfERG) response abnormalities in patients with acute central serous chorioretinopathy (CSC). METHODS: This was a cross-sectional observational study in which 45 eyes of 45 patients with acute CSC underwent mfERG recordings. Peak amplitudes and implicit times of the first and second-order kernel responses were analyzed and compared with 20 age-matched normal controls. Correlation analyses were performed between the patients' visual acuity and the first and second-order amplitudes and implicit times. RESULTS: The first-order N1 and P1 mfERG amplitudes in the central three concentric rings were reduced in eyes with acute CSC compared with controls (P < 0.05). The first-order P1 implicit times of the central four rings were also delayed (P < 0.05). For the second-order mfERG response, there were significant reductions in the second-order P1 and N1 amplitudes in rings 3-5 compared with controls (P < 0.05). No significant difference between the second-order P1 and N1 implicit times was found compared with controls (P > 0.05). Correlation analyses showed significant correlations between visual acuity and the first-order N1 response amplitudes of rings 1 and 2, and for the first-order N1 and P1 implicit times of rings 1-4 (P < 0.05). CONCLUSION: Both first and second-order mfERG response abnormalities occur in eyes with acute CSC. These results suggest that in acute CSC, while outer retinal dysfunction is mostly localized to the central macula, there might be more widespread impairment in adaptive mechanisms of the inner retina or outer plexiform layer dysfunction in the more peripheral macula.

The clinical applications of multifocal electroretinography: a systematic review.

Multifocal electroretinography (mfERG) is an investigation that can simultaneously measure multiple electroretinographic responses at different retinal locations by cross-correlation techniques. mfERG therefore allows topographic mapping of retinal function in the central 40-50 degrees of the retina. The strength of mfERG lies in its ability to provide objective assessment of the central retinal function at different retinal areas within a short duration of time. Since the introduction of mfERG in 1992, mfERG has been applied in a large variety of clinical settings. This article reviews the clinical applications of mfERG based on the currently available evidence. mfERG has been found to be useful in the assessment of localized retinal dysfunction caused by various acquired or hereditary retinal disorders. The use of mfERG also enabled clinicians to objectively monitor the treatment outcomes as the changes in visual functions might not be reflected by subjective methods of assessment. By changing the stimulus, recording, and analysis parameters, investigation of specific retinal electrophysiological components can be performed topographically. Further developments and consolidations of these parameters will likely broaden the use of mfERG in the clinical setting.

Multifocal electroretinographic changes in patients receiving hydroxychloroquine therapy.

PURPOSE: To evaluate the longitudinal changes in multifocal electroretinography (mfERG) in patients receiving hydroxychloroquine and to assess the effects of cumulative hydroxychloroquine dose on mfERG. DESIGN: Prospective cohort study. METHODS: Twenty-four eyes in 12 patients receiving hydroxychloroquine underwent mfERG recordings at baseline and 1 to 2 years later. The first negative (N1) and first positive (P1) response amplitudes and peak latencies were compared with normal controls. Serial changes in the pattern of mfERG abnormalities and in response amplitudes and peak latencies were also compared between eyes in which hydroxychloroquine therapy was continued or stopped. Correlation analyses were performed to assess the effects of a cumulative dose of hydroxychloroquine on mfERG. RESULTS: At baseline, reductions in N1 and P1 response amplitudes were observed in patients receiving hydroxychloroquine compared with controls. At follow-up, in addition to the reductions in N1 and P1 response amplitudes, increases in P1 peak latencies compared with controls were observed. In patients who stopped hydroxychloroquine therapy, there were significant increases in N1 and P1 response amplitudes at follow-up mfERG. CONCLUSIONS: Patients receiving hydroxychloroquine showed a longitudinal decline in retinal function; patients who stopped hydroxychloroquine therapy showed improvement. Although these data are insufficient to demonstrate the sensitivity of mfERG for evaluating early hydroxychloroquine toxicity, the results suggest that serial mfERG assessment may help detect early retinal changes associated with hydroxychloroquine therapy. Further studies with long-term results will be useful in clarifying the value of mfERG in evaluating early retinal toxicity due to hydroxychloroquine.

Prevalence, incidence, and progression of myopia of school children in Hong Kong.

PURPOSE: To determine the prevalence, incidence, and progression of myopia of Chinese children in Hong Kong. METHODS: A cross-sectional survey was initially conducted. A longitudinal follow-up study was then conducted 12 months later. RESULTS: A total of 7560 children of mean age 9.33 (95% confidence interval [CI] = 9.11-9.45; range, 5-16) participated in the study. Mean spherical equivalent refraction (SER) was -0.33 D (SD = 11.56; range, -13.13 to +14.25 D). Myopia (SER