Kei Shinoda

Correlation of Integrity of Cone Outer Segment Tips Line With Retinal Sensitivity After Half-dose Photodynamic Therapy for Chronic Central Serous Chorioretinopathy

PURPOSE To investigate the relationship between the integrity of the photoreceptor microstructures and retinal sensitivity after half-dose photodynamic therapy (PDT) in eyes with chronic central serous chorioretinopathy (CSC). DESIGN Prospective, noncomparative, interventional case series. METHODS Thirteen eyes of 13 patients with chronic CSC who had received half-dose verteporfin PDT were studied. The best-corrected visual acuity (BCVA), macular retinal sensitivity in the central 12 degrees, and optical coherence tomographic (OCT) findings were evaluated at baseline and at 1, 3, 6, and 12 months after the half-dose PDT. The integrities of the external limiting membrane (ELM), the inner segment/outer segment junction (IS/OS) line, and the cone outer segment tips (COST) line were determined. The retinal sensitivity was determined by MP-1 microperimetry. RESULTS The serous retinal detachment (SRD) was completely resolved in 11 eyes at 1 month and in 1 eye at 3 months. The remaining eye had a persistent SRD throughout the follow-up period. The mean retinal sensitivity was significantly better at 1, 3, 6, and 12 months after the half-dose PDT than at baseline. Before the PDT, 12 eyes had a continuous ELM and 1 eye had a fragmented ELM. The number of eyes with an intact IS/OS line and COST line increased with increasing post-PDT time. At 12 months after PDT, the IS/OS line was detected in 11 eyes and the COST line in 6 eyes. At 6 and 12 months, the retinal sensitivity was significantly higher in eyes with an intact COST line and IS/OS lines than in eyes with an intact IS/OS line only. However, no difference was found in the visual acuity of these 2 groups. The 1 eye with a persistent SRD and another eye with fragmented ELM and absent IS/OS and COST lines through the follow-up periods were associated with poor retinal sensitivity of 8.5 dB and 10.9 dB respectively. CONCLUSIONS Our findings show that there is a significant improvement in the macular sensitivity after half-dose PDT in eyes with chronic CSC. The improvement was correlated with the recovery of the IS/OS and COST lines at 6 and 12 months.

One-Year Outcomes with Half-Dose Verteporfin Photodynamic Therapy for Chronic Central Serous Chorioretinopathy

PURPOSE To assess the 1-year outcome of half-dose verteporfin photodynamic therapy (PDT) for patients with chronic central serous chorioretinopathy (CSC). DESIGN Retrospective, interventional case series with no controls. PARTICIPANTS A total of 204 eyes of 204 patients with chronic CSC were studied. METHODS Fluorescein angiography (FA) and indocyanine green angiography (ICGA) were performed before PDT. The best-corrected visual acuities (BCVAs) were measured and optical coherence tomography was performed before and 1, 3, 6, 9, and 12 months after PDT. MAIN OUTCOME MEASURES The main outcome measures were the resolution of the serous retinal detachment (SRD), changes in BCVA, and ocular and systemic complications at 12 months. RESULTS A total of 182 of 204 eyes (89.2%) had complete resolution of the SRD at 12 months after the PDT. Eleven eyes (5.4%) had a persistent SRD throughout the follow-up period, and 12 eyes (5.9%) had a recurrence of the SRD after an earlier resolution. One of the 12 eyes had a spontaneous resolution of the SRD 6 months after PDT. The mean±standard deviation BCVA in logarithm of the minimum angle of resolution (logMAR) units significantly improved from 0.11±0.25 before to 0.07±0.23 at 1 month, 0.02±0.23 at 3 months, 0.01±0.23 at 6 months, 0.00±0.24 at 9 months, and -0.01±0.22 at 12 months (P<0.0001). The eyes with an SRD at 12 months were more likely to have an intermediate hyperfluorescence on ICGA (chi-square test, P<0.001) and poorer BCVA before the half-dose PDT (Student t test, P=0.04) than those without SRD at 12 months. None of the patients developed any systemic complications or experienced any severe visual reduction after the half-dose PDT. However, polypoidal lesion appeared in 1 eye 8 months after the PDT. CONCLUSIONS Half-dose PDT is an effective and safe method to treat eyes with chronic CSC with an SRD. The CSC resolved and the BCVA improved significantly after PDT. Half-dose PDT was less effective for cases without intense hyperpermeability on ICGA and those with lower BCVA before the PDT.

Recovery of photoreceptor inner and outer segment layer thickness after reattachment of rhegmatogenous retinal detachment

Aims To evaluate the recovery of retinal function and the thicknesses of the photoreceptor inner (IS) and outer segment (OS) layers after a reattachment of a rhegmatogenous retinal detachment (RRD). Methods 49 eyes of 49 patients (mean age, 57.4±10.3 years) with successfully reattached RRD were retrospectively studied. Spectral-domain optical coherence tomography was used to obtain images of the foveal area, and the thicknesses of the IS and OS were measured before and 1, 3, 6 and 12 months after surgery. The thicknesses of the corresponding structures of the healthy fellow eye served as control. Results The thickness of the IS layer was 20.4±5.0 μm and that of the OS layer was 34.4±9.7 at 1 month after surgery, which was significantly thinner than the IS (28.9±2.9) and OS (55.4±5.2) layers of the fellow eyes. The thicknesses gradually increased and were not significantly different from that in the fellow eye at 12 months (IS, 28.4±4.4 µm and OS, 50.7±6.6 µm). The IS and OS thicknesses at 1 month after surgery in eyes that had a decimal visual acuity of 1.0 at 6 months were significantly thicker than those in eyes that had a visual acuity of <1.0. Conclusions The increase in the thicknesses of the IS and OS layers of the photoreceptors during the recovery phase of eyes with RRD indicates that the recovery process was slow and gradual. Quantitative analysis of the IS and OS thicknesses may be useful to follow the disease process.

Novel RP1L1 Variants and Genotype-Photoreceptor Microstructural Phenotype Associations in Cohort of Japanese Patients With Occult Macular Dystrophy.

PURPOSE To determine the clinical and genetic characteristics of Japanese patients with occult macular dystrophy (OMD) in a nationwide multicenter study. METHODS Twenty-three patients from 21 families with clinically diagnosed OMD were studied at 10 institutions throughout Japan. Ophthalmologic examinations including spectral-domain optic coherence tomography were performed. Patients were classified into two phenotype groups: a classical group having both blurred ellipsoid zone and absence of interdigitation zone of the photoreceptors, and a nonclassical group lacking at least one of these two features. Whole-exome sequencing, direct sequencing, and in silico molecular analysis were performed to detect the pathogenic RP1L1 variants. Statistical associations between the phenotype and genotypes based on the presence of pathogenic RP1L1 variants were investigated. RESULTS There were 12 families with the classical findings and 9 families with the nonclassical findings. Nine pathogenic RP1L1 missense variants were identified in 12 families (57%) including three reported variants, namely, p.R45W, p.S1199C, and p.G1200A, and six novel variants, p.G221R, p.T1194M, p.T1196I, p.G1200D, p.G1200V, and p.V1201G. The pathogenic missense variants in seven families (33%) were located between amino acid numbers 1196 and 1201. A significant association was found between the photoreceptor microstructural phenotypes and molecular genotypes. CONCLUSIONS The spectrum of the morphologic phenotypes and pathogenic RP1L1 variants was documented in a well-characterized Japanese cohort with OMD. A unique motif including six amino acids (1196-1201) downstream of the doublecortin domain could be a hot spot for RP1L1 pathogenic variants. The significant association of the morphologic phenotypes and genotypes indicates that there are two types of pathophysiology underlying the occult macular dysfunction syndrome: a hereditary OMD with the classical phenotype (Miyakes disease), and a nonhereditary OMD-like syndrome with progressive occult maculopathy.

Detailed analysis of family with autosomal recessive bestrophinopathy associated with new BEST1 mutation.

PurposeTo describe the clinical and genetic findings in a patient with autosomal recessive bestrophinopathy (ARB) and his healthy parents.MethodsThe patient and his healthy non-consanguineous parents underwent detailed ophthalmic evaluations including electro-oculography (EOG), spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) imaging. Mutation analysis of the BEST1 gene was performed by Sanger sequencing.ResultsThe FAF images showed multiple spots of increased autofluorescence, and the sites of these spots corresponded to the yellowish deposits detected by ophthalmoscopy. SD-OCT showed cystoid macular changes and a shallow serous macular detachment. The Arden ratio of the EOG was markedly reduced to 1.1 in both eyes. Genetic analysis of the proband detected two sequence variants of the BEST1 gene in the heterozygous state: a novel variant c.717delG, p.V239VfsX2 and an already described c.763C>T, p.R255W variant associated with Best vitelliform macular dystrophy and ARB. The proband’s father carried the c.717delG, p.V239VfsX2 variant in the heterozygous state, and the mother carried the c.763C>T, p.R255W variant in the heterozygous state. The parents who were heterozygous for the BEST1 variants had normal visual acuity, EOG, SD-OCT, and FAF images.ConclusionsIn a truncating BEST1 mutation, the phenotype associated with ARB is most likely due to a marked decrease in the expression of BEST1 promoted by the nonsense-mediated decay surveillance mechanism, and it may depend on the position of the premature termination of the codon created.

Assessment of Macular Function during Vitrectomy: New Approach Using Intraoperative Focal Macular Electroretinograms

Purpose To describe a new technique to record focal macular electroretinograms (FMERGs) during vitrectomy to assess macular function. Methods Intraoperative FMERGs (iFMERGs) were recorded in ten patients (10 eyes) who undergo vitrectomy. iFMERGs were elicited by focal macular stimulation. The stimulus light was directed to the macular area through a 25 gauge (25G) glass fiber optic bundle. Background light was delivered through a dual chandelier-type light fiber probe. Focal macular responses elicited with combinations of stimulus and background luminances were analyzed. Results A stimulus luminance that was approximately 1.75 log units brighter than the background light was able to elicit focal macular responses that were not contaminated by stray light responses. Thus, a stimulus luminance of 160 cd/m2 delivered on a background of 3 cd/m2 elicited iFMEGs from only the stimulated area. This combination of stimulus and background luminances did not elicit a response when the stimulus was projected onto the optic nerve head. The iFMERGs elicited by a 10° stimulus with a duration of 100 ms and an interstimulus interval of 150 ms consisted of an a-, b-, and d-waves, the oscillatory potentials, and the photopic negative response (PhNR). Conclusions Focal ERGs with all components can be recorded from the macula and other retinal areas during vitreous surgery. This new technique will allow surgeons to assess the function of focal areas of the retina intraoperatively.

Intraoperative electrophysiological evaluations of macular function during peripheral scleral indentation

Scleral indentation is widely used to examine the peripheral fundus, however it can increase the intraocular pressure (IOP) to high levels which can then affect retinal function. We evaluated the effects of scleral indentation on the macular function electrophysiologically. Intraoperative focal macular electroretinograms (iFMERGs) were recorded with and without controlling the IOP in 7 eyes. Without IOP control, the IOP increased from 21.7 ± 4.9 to 92.7 ± 20.2 mmHg significantly (P = 0.020) and the amplitudes of the b-wave (from 6.29 ± 1.160 to 3.71 ± 1.98 uV, P = 0.007), on-photopic negative response (from 2.29 ± 0.99 to 0.72 ± 0.47 uV, on-PhNR, P = 0.005), and d-wave (from 2.57 ± 0.41 to 1.64 ± 0.69 uV, P = 0.007) decreased significantly soon after beginning the indentation. All values returned to the baseline levels after releasing the indentation. In the eyes with IOP controlled, the IOP and the amplitude of all components did not change significantly during and after the indentation except the on-PhNR amplitude which was significantly reduced during the indentation. The changes in the iFMERGs and macular function caused by scleral indentation were transient and reversible. The changes can be minimized by controlling the IOP.

Electroretinographic evaluations of retinal function before, just after, and after intravitreal injections.

Intravitreal injections (IVI) have become a part of daily practice for a growing number of procedures. We evaluated the retinal function by recording intraoperative photopic electroretinograms (ERGs) before an injection (T1), just after the injection (T2), and after the aspiration of the anterior chamber fluid (T3) of 19 eyes of 19 patients (mean age 70.6 years; men = 11) who received an IVI of an anti-vascular endothelial growth factor. The mean amplitudes of the b-wave, photopic negative responses (PhNR), and oscillatory potentials (OPs) 1 and 2 at T2 were significantly smaller than that at T1, but no significant difference was observed between T3 and T1. The mean implicit times of the a-wave and OP1, 2, and 3 at T2 and the a-wave and the OP2 at T3 were significantly longer than that at T1. The mean intraocular pressure (IOP) at T2 (49.32 mm Hg) was significantly higher and the IOP at T3 (8.74 mm Hg) was significantly lower than that at T1 (21.05 mm Hg). The retinal function was reduced and the IOP elevated just after the IVI. The response of each ERG component was different suggesting a different sensitivity of each type of retinal neuron to IVI.

Intraoperative Electroretinograms before and after Core Vitrectomy.

Purpose To evaluate retinal function by intraoperative electroretinograms (ERGs) before and after core vitrectomy. Design Retrospective consecutive case series. Method Full-field photopic ERGs were recorded prior to the beginning and just after core vitrectomy using a sterilized contact lens electrode in 20 eyes that underwent non-complicated vitreous surgery. A light-emitted diode was embedded into the contact lens, and a stimulus of 150 ms on and 350 ms off at 2 Hz was delivered. The amplitudes and latencies of the a-, b-, and d-waves, photopic negative response (PhNR), and oscillatory potentials (OPs) were analyzed. The intraocular temperature at the mid-vitreous was measured at the beginning and just after the surgery with a thermoprobe. Results The intraocular temperature was 33.2 ± 1.3°C before and 29.4 ± 1.7°C after the vitrectomy. The amplitudes of the PhNR and OPs were significantly smaller after surgery, and the latencies of all components were prolonged after the surgery. These changes were not significantly correlated with the changes of the temperature. Conclusion Retinal function is reduced just after core vitrectomy in conjunction with significant temperature reduction. The differences in the degree of alterations of each ERG component suggests different sensitivity of each type of retinal neuron.

Binocular interaction of visually evoked cortical potentials elicited by dichoptic binocular stimulation

To analyze the interaction of cortical potentials elicited by dichoptic stimulation of the dominant and fellow eyes at different frequencies, a pair of programmed power supply units were used to drive a light emitting diode (LED) mounted in the right and left eyes of light-proof goggles to elicit the visually evoked cortical responses (VECPs). The right eye was stimulated at 11.5 Hz and the left eye at 11.0 Hz. Then the stimulation was repeated with the frequency of stimulation switched to the other eyes. The stimulus duration was 5 ms. The sampling rate was 1.0 Hz, and the duration of collection was 200 ms. The VECP of each eye was extracted separately. Individual VECPs could be recorded separately after simultaneous dichoptic stimulation of each eye. The amplitudes of the VECPs were not significantly different after stimulating the dominant eye and the fellow eye separately. The implicit times of negative peak (N-2) and the second positive peak (P-2) were shorter after stimulation of the dominant eye than after stimulation of the fellow eye, but the difference was not significant. However, the implicit time of N-2 elicited by stimulating the dominant eye was significantly shorter when the stimulation rate was 11.5 Hz. The VECPs elicited by stimulating the two eyes can be recorded separately by simultaneous dichoptic stimulation. Dichoptic simultaneous stimulation required a shorter time and may be a more sensitive method of analyzing binocular interactions compared to the classic VECPs using monocular stimulation.