Ricky Y. K. Lai

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/m2) 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.

Safety enhanced photodynamic therapy with half dose verteporfin for chronic central serous chorioretinopathy: a short term pilot study.

Aim: To evaluate short term safety of an enhanced photodynamic therapy (PDT) protocol with half dose verteporfin for treating chronic central serous chorioretinopathy (CSC). Methods: 20 eyes of 18 patients with symptomatic chronic CSC underwent PDT using 3 mg/m2 verteporfin. Verteporfin was infused over 8 minutes followed by indocyanine green angiography guided laser application 2 minutes later. Serial optical coherence tomography (OCT) and multifocal electroretinography (mfERG) recordings were performed before PDT, at 4 days, 2 weeks, and 1 month after PDT. The best corrected visual acuity (BCVA), OCT central retinal thickness, and mean mfERG response amplitudes and peak latencies were compared longitudinally. Subgroup analysis was further performed for eyes with or without pigment epithelial detachment (PED). Results: At 1 month after PDT, the median BCVA improved from 20/40 to 20/30 (p = 0.001). The mean central retinal thickness also reduced from 276 μm to 158 μm (p<0.001) and 17 (85%) eyes had complete resolution of serous retinal detachment and/or PED. MfERG showed no significant changes in the mean N1 and P1 response amplitude and latency for all eyes. Subgroup analysis demonstrated that eyes without PED had a significant increase in the mean central mfERG P1 response amplitude with reduction in P1 peak latency at 1 month post-PDT. For eyes with PED, transient reduction in the mean central P1 response amplitude was observed at 4 days post-PDT. Conclusions: The modified safety enhanced PDT protocol with half dose verteporfin appeared to be a beneficial treatment option for patients with chronic CSC, especially in eyes without serous PED. Further controlled study is warranted to demonstrate the long term safety and efficacy of this treatment option.

Anterior chamber angle measurement with anterior segment optical coherence tomography: a comparison between slit lamp OCT and Visante OCT.

PURPOSE To compare anterior chamber angle measurements obtained from two anterior segment optical coherence tomography (OCT) instruments and to evaluate their agreements and interobserver reproducibility. METHODS Forty-nine eyes from 49 healthy normal subjects were studied. The anterior chamber angle was imaged with the Visante anterior segment OCT (Carl Zeiss Meditec, Dublin, CA) and the slit lamp OCT (SLOCT, Heidelberg Engineering, GmbH, Dossenheim, Germany) on one randomly selected eye in each subject and measured by two independent observers. The angle-opening distance (AOD 500), the trabecular-iris angle (TIA 500), and the trabecular-iris space area (TISA 500) at the nasal and temporal angles were measured. The agreements between SLOCT and Visante OCT measurements and the interobserver reproducibility were evaluated. RESULTS The mean nasal/temporal anterior chamber angles measured by Visante OCT and SLOCT were 527 +/- 249/572 +/- 275 microm (AOD), 0.180 +/- 0.091/0.193 +/- 0.102 mm(2) (TISA), and 38.1 +/- 12.3/39.6 +/- 13.2 degrees (TIA); and 534 +/- 234/628 +/- 254 microm (AOD), 0.191 +/- 0.089/0.217 +/- 0.093 mm(2)(TISA), and 37.8 +/- 10.1/40.6 +/- 10.7 degrees (TIA), respectively. No significant difference was found between Visante OCT and SLOCT measurements except the temporal TISA (P = 0.034). The interobserver coefficient of variation ranged between 4.4% and 7.8% for Visante OCT and 4.9% and 7.0% for SLOCT. The spans of 95% limits of agreement of the nasal/temporal angle measurements between Visante OCT and SLOCT were 437/531 mm(2), 0.174/0.186 mm(2), and 25.3/28.0 degrees for AOD, TISA, and TIA, respectively. CONCLUSIONS Although Visante OCT and SLOCT demonstrate high interobserver reproducibility for anterior chamber angle measurements, their agreement was poor.

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.This study explored the association of 14 single nucleotide polymorphisms in three genes coding for influx transporters (SLC22A1, SLCO1B1, and SLCO1B3), two genes coding for efflux transporters (ABCB1 and ABCG2), and four genes coding for enzymes (CYP2C9, CYP2C19, CYP2D6, and CYP3A5) with the pharmacokinetics of imatinib in Japanese patients with chronic myeloid leukemia. Pharmacokinetic parameters were estimated by a population pharmacokinetic analysis based on 622 plasma samples from 34 patients at steady state. Approximately 4.6-fold variability in individual clearance was observed (range, 3.4-15.5 L/hr). The individual estimated clearance was significantly increased in patients with the SLCO1B3 334GG genotype (median value ± standard deviation, 9.5 ± 3.1 L/hr; n = 19) compared with SLCO1B3 334TT and TG genotypes (7.0 ± 3.1 L/hr; n = 15) (P = 0.019). Patients with the ABCB1 3435CC genotype had significantly higher imatinib clearance (12.7 ± 3.0 L/hr; n = 7) compared with patients with ABCB1 3435CT and TT genotypes (7.9 ± 2.7 L/hr; n = 27) (P = 0.035). In conclusion, the present study suggests that single nucleotide polymorphisms of the influx transporter SLCO1B3 and the efflux transporter ABCB1 were functionally associated with individual variability of imatinib pharmacokinetics in Japanese patients with chronic myeloid leukemia.

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.

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.

Multifocal electroretinography changes in patients on ethambutol therapy

PurposeTo evaluate the multifocal electroretinography (mfERG) changes in patients on ethambutol therapy.MethodsA cross-sectional observational study of 17 visually asymptomatic patients receiving antituberculosis therapy with ethambutol. Patients underwent complete ophthalmic examination and mfERG recordings. The first-order mfERG N1 and P1 response amplitudes and implicit times of six concentric rings were analysed and compared with 17 normal age-similar controls. Correlation analyses were performed between the patients’ mfERG parameters with parameters of ethambutol usage (daily dose of ethambutol per body weight, duration of ethambutol therapy, cumulative dose of ethambutol, and cumulative dose of ethambutol per body weight).ResultsThe mean duration of ethambutol therapy was 3.6 months (range: 2–9 months) and the mean daily dose per body weight was 13.2 mg/kg/day. Analysis of response amplitude measures showed no significant difference in the mfERG N1 and P1 response amplitudes between the ethambutol and control groups at all ring eccentricities (P>0.05). For implicit times, there were significant delays in the mfERG P1 implicit times of rings 4–6 in the ethambutol group compared with controls (P=0.012 to P=0.041). Correlation analyses showed no significant correlation between the mfERG and ethambutol parameters (P>0.05).ConclusionsThe mfERG findings suggested that visually asymptomatic patients receiving ethambutol therapy might have localized mild electrophysiological changes involving the peripheral macula. These changes might be related to localized alteration of metabolism or physiological changes associated with ethambutol therapy.

Multifocal electroretinography in dengue fever-associated maculopathy

Dengue fever is a viral disease transmitted by Aedes mosquitoes and is endemic in the tropics.1 The severity of dengue fever varies from mild non-specific febrile illness to potentially fatal dengue haemorrhagic fever causing thrombocytopenia and shock. Patients with dengue fever may develop various ophthalmic manifestations causing visual loss, including macular oedema, macular haemorrhage, retinal vasculitis, “cotton-wool” spots and optic disc swelling.2–8 We report the use of multifocal electroretinography (mfERG) in the assessment of a patient with dengue fever-associated maculopathy in whom there were no clinical or angiographic abnormalities. A 16-year-old girl with serologically confirmed dengue fever presented with left relative scotoma and reduced vision 7 days after the onset of fever. Her visual acuity was 20/20 …

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

PurposeTo 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.MethodsTwenty-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.ResultsThe 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).ConclusionIn 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.