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Inherited retinal diseases (IRDs) comprise a phenotypically and genetically heterogeneous group of ocular disorders that cause visual loss via progressive retinal degeneration. Here, we report the genetic characterization of 1210 IRD pedigrees enrolled through the Japan Eye Genetic Consortium and analyzed by whole exome sequencing. The most common phenotype was retinitis pigmentosa (RP, 43%), followed by macular dystrophy/cone- or cone-rod dystrophy (MD/CORD, 13%). In total, 67 causal genes were identified in 37% (448/1210) of the pedigrees. The first and second most frequently mutated genes were EYS and RP1, associated primarily with autosomal recessive (ar) RP, and RP and arMD/CORD, respectively. Examinations of variant frequency in total and by phenotype showed high accountability of a frequent EYS missense variant (c.2528GA). In addition to the two known EYS founder mutations (c.4957dupA and c.8805CG) of arRP, we observed a frequent RP1 variant (c.5797CT) in patients with arMD/CORD.

Purpose. To determine the effects of cataract surgery on contrast visual acuity and retinal sensitivity in patients with retinitis pigmentosa. Methods. Retinal sensitivity and contrast visual acuity were determined by microperimetry (MAIA) and contrast sensitivity acuity tester (CAT-CP), respectively, before and after cataract surgery. The significance of the correlations between visual acuity, retinal sensitivity, contrast visual acuity, improvements after surgery, and macular structure before and after cataract surgery was determined. Results. Retinal sensitivity and contrast visual acuity were significantly improved after cataract surgery. The correlations among postoperative visual acuity, postoperative retinal sensitivities, and preoperative ellipsoid zone length were significant. The postoperative retinal sensitivity of the central 10° and the ellipsoid zone length was particularly significantly correlated. Preoperative contrast visual acuity and the amount of improvement and preoperative retinal sensitivity and the amount of improvement were significantly negatively correlated. The contrast visual acuity under both the 100% and 10% photopic and mesopic conditions improved significantly after cataract surgery. Conclusions. Cataract surgery in retinitis pigmentosa patients with preserved ellipsoid zones significantly improved retinal sensitivity and contrast visual acuity. Cataract surgery can be expected to improve retinal sensitivity and contrast visual acuity under various conditions, even if preoperative visual parameters are low, as long as the ellipsoid zone is preserved.

Purpose. To determine the effects of cataract surgery and preoperative factors on the vision-related quality of life (QOL) in patients with retinitis pigmentosa (RP). Materials and Methods. This was a prospective, interventional study of 54 patients diagnosed with RP. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was used to determine the QOL before and after the cataract surgery. The correlations between the scores of the questionnaire and the best-corrected visual acuity (BCVA), macular structure, and degree of improvement of the NEI VFQ-25 scores were also determined. Results. Statistically significant improvements were observed in the BCVA and all of the NEI VFQ-25 subscale scores except for color vision. The improvement of general vision was the largest. The postoperative BCVA of the better-seeing eye was more strongly and significantly correlated with the postoperative NEI VFQ-25 scores than that of the worse-seeing eye. All of the postoperative NEI VFQ-25 scores were significantly correlated with the length of the ellipsoid zone (EZ) of the photoreceptors. No significant correlation was found between the preoperative general vision, near vision, mental health scores, and EZ length. All of the preoperative NEI VFQ-25 scores except the social function and mental health scores were negatively and significantly correlated with the degree of improvement of the NEI VFQ-25 score. The EZ length was significantly correlated with the degree of improvement of the NEI VFQ-25 scores of the general vision, distance vision, mental health, dependency, and composite 9 scores. Conclusions. Cataract surgery can significantly improve the NEI VFQ-25 scores in RP patients. The EZ length can be used to predict the postoperative VFQ scores. We conclude that the NEI VFQ-25 is a useful method to evaluate the impact of cataract surgery on the BCVA in patients with RP.

Purpose. To report a case of persistent fetal vasculature (PFV) with a retinal detachment that worsened after cataract surgery. Pars plana vitrectomy (PPV) was performed which reduced the vitreous traction and reattached the retina. Observations. A 20-year-old Myanmarese woman presented with a mature cataract, and her vision was light perception. She underwent uneventful cataract surgery with implantation of an intraocular lens. Her visual acuity improved to 20/200 immediately after the surgery. However, fibrotic tissue was observed between the optic nerve head and the posterior capsule. She was diagnosed with PFV, and she was followed without any intervention. One and a half years after the cataract surgery, she had an advanced retinal detachment which extended over the inferior two quadrants. Her vision deteriorated to 20/400. She underwent PPV, and the PFV tissue was removed which resulted in the reattachment of the retina. The visual acuity improved to 20/60. Conclusions. Surgeons should be aware that it is possible to worsen a retinal detachment after cataract surgery in the eyes with PFV. A simple technique to release the anterior-posterior traction by the PPV was sufficient to achieve the reattachment of the retina.

The purpose of this study was to evaluate the long-term effects of half-time photodynamic therapy (PDT) on the retinal sensitivity in eyes with chronic central serous chorioretinopathy (CSC). Twenty-two eyes of 22 patients with chronic CSC were studied. PDT was applied with full-dose verteporfin and half-time laser duration. The best-corrected visual acuity (BCVA) and retinal sensitivity in the central 2 and 10 degrees were evaluated at the baseline, and at 12 and 24 months after the half-time PDT. The retinal sensitivity was determined by Macular Integrity Assessment microperimetry (MAIA, Centervue, Padova, Italy). The results showed that the mean retinal sensitivities in the central 2 and 10 degrees were significantly improved at 12 months (25.6±2.79 dB, median; 26.11 dB, 25.6±2.25 dB, median; 25.65 dB, respectively; P<0.001) and at 24 months (26.3±2.62 dB, median; 27.38 dB, 26.6±2.21 dB, median; 27.45 dB, respectively; P<0.001) after the treatment compared to that at the baseline (19.2±3.93 dB, median; 19.34 dB, 20.9±2.92 dB, median; 20.9 dB, respectively). The BCVA was also significantly improved from 0.18±0.19 median; 0.15 logarithm of the minimum angle of resolution (logMAR) units at the baseline to 0.07±0.15 median; 0 logMAR units at 12 months (P<0.001) and to 0.049±0.16 median; -0.039 logMAR units at 24 months (P<0.001). We conclude that half-time PDT results in a significant improvement of the mean central retinal sensitivity for at least 24 months in eyes with chronic CSC. Thus, half-time PDT is beneficial in resolving chronic CSC for a relatively long period.

Macular hole has been believed to be a disorder of vitreomacular interface, which forms as a result of abnormal vitreous traction from incomplete vitreous detachment. However, our recent studies demonstrated that dynamic forces, caused by mobile posterior cortical vitreous with fluid currents, exist already at early stages of macular hole development. Therefore, in eyes with flexible vitreous, the contributions of tractional forces due to vitreous shrinkage are unlikely. These facts indicate that in the development of idiopathic macular holes, there is a greater contribution of dynamic forces than has been previously reported. This review also evaluates the recent findings in the assessment of the idiopathic macular holes and the recent therapeutic strategies for optimal management. Inner limiting membrane is considered to improve anatomical closure rate; however, it is still questionable if peeling is necessary in holes less than 250 µm. There are plenty of publications indicating that in the management of small and medium size hole (less than 400 µm), use of long-lasting gas and face-down position is not always required; however, it may be necessary for the treatment of large holes. Ocriplasmin and expansile gas had been reported to be successful for management of small- and medium-sized holes and vitreomacular attachment.

The purpose of this study was to compare the efficacies of one initial intravitreal injection of aflibercept followed by a pro re nata (PRN; 1+PRN) regimen to those of three consecutive monthly injections followed by the PRN (3+PRN) regimen for diabetic macular edema (DME) with practical protocols. The medical records of 95 eyes of 71 cases that were diagnosed with DME and had received intravitreal aflibercept (IVA) injections were reviewed. Fifty-seven eyes had received IVA with the 1+PRN regimen, and 38 eyes had received IVA with the 3+PRN regimen. The best-corrected visual acuity (BCVA) and the central macular thickness (CMT) were measured at the baseline and at 1, 3, 6, and 12 months after the IVA. The mean number of injections of the 1+PRN group was 2.9 ± 1.7 , which was significantly fewer than that of the 3+PRN group at 4.6 ± 1.4 ( P < 0.001 ). The change of the mean BCVA before and after the IVA at 12 months of the 3+PRN group was − 0.14 ± 0.17 logMAR units which was significantly better than that of the 1+PRN group of − 0.045 ± 0.25 logMAR units ( P = 0.02 ). The change of the CMT before and after the IVA at 6 months of the 3+PRN group was − 141.3 ± 152.4 μ m which was significantly more than that of the 1+PRN group at − 86.1 ± 117.8 μ m ( P = 0.013 ). Although the mean number of injections was more than that in the 1+PRN regimen, the 3+PRN regimen had better visual outcomes at 12 months. In a practical protocol, we recommend the 3+PRN regimen for patients with DME (IRB#3541).

A 37-year-old Japanese man had his right eye hit by a fist. His right eye developed hypotony maculopathy and secondary cataract, and his visual acuity decreased to 20/200 with an intraocular pressure of 4 mmHg. He underwent phacoemulsification and aspiration, implantation of the intraocular lens, and encircling with a silicone tire. His visual acuity improved to 20/20 and stable for more than one year postoperatively. The intraocular pressure in his right eye increased to 12 mmHg, and maculopathy was resolved entirely. It was suggested that an encircling buckle obstructed the uveoscleral outflow through the cyclodialysis and increased intraocular pressure. Concurrent cataract surgery and encircling was sufficient to improve the vision.

A 61-year-old Japanese woman presented with impairment of her left vision due to macular schisis secondary to branch retinal vein occlusion. Her left vision was 20/50, and schisis was observed inferotemporally. She underwent phacoemulsification and aspiration, implantation of the intraocular lens, and removal of the epiretinal membrane and internal limiting membrane. Her visual acuity stabilized ~20/50 for two and a half years after the initial surgery. However, she developed macula-involving retinal detachment, and her visual acuity declined to counting fingers. She underwent pars plana vitrectomy and removal of the residual vitreous cortex together with the inner retina within the area of vein occlusion. After the removal of silicone oil and the addition of an encircling buckle, the retina remained attached and visual acuity improved to 20/60 at one year after the final surgery. The combination of rhegmatogenous and tractional detachment in the area of schisis was suspected, and vitrectomy with inner retinectomy was effective.

Purpose. Diabetic macular edema (DME) is a vision-threatening condition that develops in diabetic patients. The first-line therapy for DME is intravitreal injections of antivascular endothelial growth factor (anti-VEGF) agents; however, the high frequency of repeat injections, invasiveness of the procedure, and high cost are drawbacks for this treatment. The purpose of this report is to present our findings in 3 patients with chronic DME whose edema was resolved soon after oral doses of sodium-glucose cotransporter-2 (SGLT2) inhibitors were used. Case Presentation. Case 1 was a 66-year-old woman diagnosed with moderate nonproliferative diabetic retinopathy (DR) with DME that had developed a decade earlier. The DME persisted for 4 years in the left eye. The addition of oral empagliflozin, a SGLT2 inhibitor, led to a marked improvement of the DME after one month, and this improvement continued over two years. Case 2 was a 68-year-old woman who was diagnosed with preproliferative DR with bilateral DME. The addition of oral dapagliflozin led to the improvement of the DME after two months, and this improvement continued over one year. Case 3 was a 61-year-old woman who was diagnosed with moderate nonproliferative DR with DME. Oral luseogliflozin was given which led to better glycemic control, and her left central retinal thickness (CRT) was markedly reduced after only two weeks. This reduction was maintained in her left eye for six months without any additional ophthalmic procedures. Conclusions. Although this study involved only three cases, our findings indicate that SGLT2 inhibitors might have possible efficacy for chronic DME.

Purpose. To investigate the annual progression of retinitis pigmentosa (RP) by changes in retinal sensitivity and length of photoreceptor microstructures. Method. The medical records of patients with typical RP followed at Chiba University Hospital were reviewed. The retinal sensitivity was measured by Micro Perimeter-1, and the lengths of the intact external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ) were measured by spectral-domain optical coherence tomography. The baseline values and annual progression rates were determined. The significance of the correlations among these factors was determined by generalized estimating equation regression analysis. Results. Forty-six eyes of 24 patients who were examined over a mean follow-up period of 3 years were studied. The annual changes in the retinal sensitivity (p = 0.0035) and the lengths of the EZ (p = 0.037) and IZ (p = 0.0033) were significantly correlated with their baseline values. The annual change in the retinal sensitivity was significantly correlated with the length of the EZ at the baseline (p = 0.020). Conclusions. The significant correlation between the annual progression of the retinal sensitivity and the baseline retinal sensitivity and lengths of the EZ and IZ in patients with RP indicate that the retinal sensitivity, the EZ, and the IZ can be useful parameters to predict the annual progression of RP.

A 17-year-old male presented with acute bilateral paracentral scotomata and blurred vision. Funduscopic examination showed bilateral macular serous retinal detachment and yellow-white placoid lesions at the level of retinal pigment epithelium. OCT study showed typical VKH disease findings with marked choroidal thickening and macular serous retinal detachment partly with subretinal septa in both eyes. FA demonstrated hypofluorescence at the placoid lesions in the early phase and hyperfluorescence in the late phase. Laboratory investigation showed negative result for HLA-DR4 serotype and the patient’s cerebrospinal fluid test values were within normal range. We made the diagnosis of APMPPE from these results. At 2-month follow-up without the use of corticosteroids, OCT reexamination showed complete amelioration of subretinal fluid in both eyes. Patchy pigmentary lesions also resolved clinically with partial chorioretinal scars. The results in this case suggested OCT findings in APMPPE patients could be similar to characteristic features usually found in acute VKH disease. We recommend comprehensive assessments such as FA, cerebral spinal fluid analysis, and HLA typing which help in leading proper diagnosis.

Purpose. To compare the visual and surgical outcomes after a reuse or a replacement of a dislocated in-the-bag intraocular lens (IOL). Methods. This was a retrospective, nonrandomized case series at a single ophthalmological institution. Cases with an in-the-bag dislocation of an IOL were treated by pars plana vitrectomy and the reuse or the replacement of the IOL. The lens was held by intrascleral fixation of the haptics of the IOL under both conditions. The same dislocated IOL was reused in 6 eyes (group A) or it was replaced with another IOL in the other 9 eyes (group B). The pre- and postoperative parameters analyzed included the visual acuity, refractive error, corneal endothelial cell density, and intraocular pressure (IOP). Results. There was no significant difference between the two groups in the postoperative visual acuity (P=0.388), refractive error (P=0.955), IOP (P=0.529), and endothelial cell loss (P=0.940). A breakage or a tilting of the IOL was observed and required replacement in three eyes in the reuse group (P=0.044). Conclusions. Half of the cases with reused in-the-bag dislocated IOL had a breakage or a tilting of the IOL. The replacement of the in-the-bag dislocated IOL is better than the reuse of the IOL with intrascleral haptics fixation.

We compared the efficacy of intravitreal aflibercept (IVA) to intravitreal ranibizumab (IVR) injections in eyes with diabetic macular edema (DME). The medical records of 49 eyes of 36 patients who were diagnosed with DME and had received IVR and 46 eyes of 40 patients who had received IVA treatment were reviewed. The central macular thickness (CMT) and best-corrected visual acuity (BCVA) were measured at the baseline and at 1, 3, and 6 months after the IVR or IVA. The mean number of injections of IVR was 2.6±1.1 and of IVA was 2.7±1.4. At 6 months, the CMT was significantly thinner than the baseline after IVR and after IVA. The mean BCVA was significantly better than the baseline after IVR only at 1 and 3 months and after IVA at 1 and 6 months. The BCVA of eyes with serous retinal detachment (SRD) was significantly better at 1 month after the IVR and at 1 month and 6 months after the IVA. The BCVAs improved more significantly in the SRD+ group than in the SRD− group. The effects of IVA persist longer than that of IVR. The effectiveness of both IVR and IVA was not dependent on the presence of SRD (IRB#2107).

Conjunctival amyloidosis is a very rare disease, and its presence may be a sign of systemic amyloidosis. We present our ocular and systemic findings in a patient with conjunctival amyloidosis. A 43-year-old man had repeated subconjunctival hemorrhages (SCHs) for two years and was referred to the Chiba University Hospital. He had comprehensive ophthalmological and systemic examinations to determine the cause of the SCHs. His visual acuities were 1.2 OU, and the intraocular pressures were 13-14 mmHg OU. Magnetic resonance imaging was normal. Initially, the SCH was the only abnormality. After 3 months, the SCH had partially cleared, and a pink mass was detected in the superior area of the subconjunctiva. Partial biopsy and histopathological examinations showed a greenish birefringence and dichroism under polarized light illumination. The birefringence was located in amyloid fibers. Immunofixation electrophoresis detected λ-light chain abnormality in the ocular biopsy specimen but systemic examinations did not find any lesions. Multiple myeloma was ruled out, and the patient is being followed closely to detect any early signs of systemic amyloidosis. Because repeated SCHs might be initial signs of systemic amyloidosis, patients with conjunctival amyloidosis should be comprehensively examined for systemic amyloidosis because of its poor life prognosis.

Archaeal 16S rRNA gene compositions and environmental factors of four distinct solfataric acidic hot springs in Kirishima, Japan were compared. The four ponds were selected by differences of temperature and total dissolved elemental concentration as follows: (1) Pond-A: 93°C and 1679 mg L−1, (2) Pond-B: 66°C and 2248 mg L−1, (3) Pond-C: 88°C and 198 mg L−1, and (4) Pond-D: 67°C and 340 mg L−1. In total, 431 clones of 16S rRNA gene were classified into 26 phylotypes. In Pond-B, the archaeal diversity was the highest among the four, and the members of the order Sulfolobales were dominant. The Pond-D also showed relatively high diversity, and the most frequent group was uncultured thermoacidic spring clone group. In contrast to Pond-B and Pond-D, much less diverse archaeal clones were detected in Pond-A and Pond-C showing higher temperatures. However, dominant groups in these ponds were also different from each other. The members of the order Sulfolobales shared 89% of total clones in Pond-A, and the uncultured crenarchaeal groups shared 99% of total Pond-C clones. Therefore, species compositions and biodiversity were clearly different among the ponds showing different temperatures and dissolved elemental concentrations.

With recent development of spectral-domain optical coherence tomography (SD-OCT), the pathological changes of retina can be observed in much greater detail. SD-OCT clearly delineates three highly reflective lines in the outer retina, which are external limiting membrane (ELM), photoreceptor inner and outer segment (IS/OS) junction, and cone outer segment tips (COST) in order from inside. These lines can serve as hallmarks for the evaluation of photoreceptor condition. In retinitis pigmentosa (RP) leading to photoreceptor degeneration, the ELM, IS/OS, and COST lines are shortened with the progression of the disease. In addition, shortening of the ELM, IS/OS and COST lines is significantly associated with each other. The line length is longest in the ELM, followed by the IS/OS, and COST, suggesting that retinal layer becomes disorganized first at the COST, followed by the IS/OS and finally the ELM. This finding is consistent with the previous report that the earliest histopathological change in RP is a shortening of the photoreceptor outer segments. On the other hand, retinal layer becomes restored first at the ELM, followed by the IS/OS and finally the COST after macular hole surgery. There may be a directionality of photoreceptor impairment or restoration on optical coherence tomographic image.

Diabetic neuropathy is associated with neurotrophic ulcerations of the skin and cornea. Decreased corneal sensitivity and impaired innervation lead to weakened epithelial wound healing predisposing patients to ocular complications such as corneal infections, stromal opacification, and surface irregularity. This review presents recent findings on impaired corneal innervation in diabetic individuals, and the findings suggest that corneal neuropathy might be an early indicator of diabetic neuropathy. Additionally, the recent findings for neuroprotective and regenerative therapy for diabetic keratopathy are presented.

A 52-year-old Japanese woman presented with optical symptoms, including left-sided myodesopsia, blurred vision, narrowed visual field, and diminished visual acuity. Ocular evaluation revealed a metastatic tumor in the choroid. Further examinations identified pulmonary adenocarcinoma as the primary tumor. Because an epidermal growth factor receptor gene (EGFR) mutation was detected in a biopsy specimen, gefitinib treatment was initiated. Dramatic responses were obtained in the primary tumor and metastatic foci. Optical symptoms improved and remained stable for 5 months during the treatment, until relapse. This report demonstrates that gefitinib is effective for choroidal metastasis of pulmonary adenocarcinoma harboring anEGFRmutation.

Although multicentric Castleman disease is a rare but life-threatening disease, eye complications are extremely uncommon. We present a case of refractory uveitis accompanied with Castleman disease successfully treated with tocilizumab. A 58-year-old man with Castleman disease was introduced for refractory uveitis to Chiba University Hospital. Large cells were detected in the anterior chamber and increased vascular permeability of retinal vessels has been found in both eyes. Although the patient was treated with oral and eye drop steroid treatment, the uveitis symptoms had not decreased. The serum levels of CRP and IL-6 were increased. The level of IL-6 concentration in the anterior chamber was the same as the serum level of IL-6. The humanized anti-IL-6 receptor-antibody (tocilizumab) was administrated for the patient because of poor general condition. After tocilizumab treatment, large cells in the anterior chamber were undetectable and vascular permeability was improved in FA. The serum levels of CRP and IL-6 decreased and the general condition improved. The side effect of tocilizumab was not observed during the treatment. Tocilizumab treatment was significantly effective for uveitis accompanied with Castleman disease. Although it is extremely rare, uveitis accompanied with Castleman disease may be one of the hallmarks to consider tocilizumab treatment.

We present our findings in a case of primary neuroendocrine carcinoma (NEC) of the lacrimal gland and a case of primary Merkel cell carcinoma (MCC) of the eyelid. An 86-year-old man noticed a swelling of the left upper eyelid three months earlier. We performed excision biopsy and histopathological examination indicated that he had a primary NEC of the left lacrimal gland. He underwent chemotherapy followed by excision including the clinically visible margins and 50 Gy radiotherapy of the surgical margins. He had neither recurrence nor metastasis for 6 months since the last radiotherapy. An 80-year-old man noticed a nodule in the right upper eyelid and was referred to our hospital because the size was increasing rapidly. A complete surgical excision of the margins of the tumor was performed with histopathological confirmation of negative margins. The final diagnosis was a primary MCC of the right upper eyelid. After surgery, he underwent 50 Gy radiotherapy on the neck to prevent metastasis. No recurrence or metastasis was found for two years. Although primary NEC of the ocular adnexa is extremely rare, the tumor has high malignancy and readily metastasizes. Thus, combined therapy including surgery, radiotherapy, and/or chemotherapy is needed for complete management of NEC.

The purpose of this report is to present the findings in a case of squamous cell carcinoma (SCC) of the conjunctiva which was the initial sign of systemic cancers. A 94-year-old woman without known systemic diseases developed a mass in her right conjunctiva. She was referred to our hospital 5 months after the onset. She was diagnosed with conjunctival SCC by biopsy. Systemic CT before the surgery revealed multiple liver lesions, lung legions, and a large mass surrounding the appendix. The patient requested the surgery, and the main aim of the surgery was cosmesis. Histopathological examinations of the specimen led us to the final diagnosis as SCC. She did not receive any other therapy because of her age. As no other surgical procedures were undertaken, it is uncertain as to whether the conjunctival lesion was primary or secondary. Although, it is extremely rare that SCC of the conjunctiva is the initial sign of systemic cancers, careful systemic examinations to find other cancers should be made.