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Background/aimsThe accuracy of pattern deviation (PD) in estimating the damage to the glaucomatous visual field (VF) in the central 10° in eyes with glaucoma and cataract is unclear.MethodsThis retrospective study includes 63 eyes of 52 glaucoma patients who successfully underwent cataract surgery or cataract surgery plus iStent implantation. Using the Humphrey Field Analyser 10–2 test, VF was measured within 6 months preoperatively and postoperatively (VFpreand VFpost, respectively). The mean total deviation values in VFpost(mTDpost) indicates glaucomatous damage without cataract and the difference between this value and mean PD values in VFpre(mPDpre) was evaluated (εmPD). The effect of cataract was then evaluated as the difference between mTDpostand mTDpre(ΔmTD), while the effects of mTDpostand ΔmTD on εmPD were also assessed. In addition, based on preoperative visual acuity (VApre) and VFpre, the optimal model for predicting mTDpostwas identified. The error of this method (εOptimalModel) was estimated as the difference against mTDpost, which was compared with εmPD.ResultsCompared with mTDpre, there was a significant improvement in mTDpost(p=0.028). A significant difference was observed between mPDpreand mTDpost(p<0.001). Further, εmPD significantly increased with the increase of mTDpostor ΔmTD (p<0.001 and p=0.0444, respectively). The absolute εOptimalModel was significantly smaller than the absolute εmPD (p<0.001).ConclusionsThis study warns clinicians that PD of the central 10° VF might underestimate the glaucomatous VF damage with the progression of glaucoma and overestimate it as a cataract progresses.

To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody.

Purpose: To describe the optical coherence tomography findings of retinal astrocytic hamartoma of tuberous sclerosis and to confirm the association between the type of retinal astrocytic hamartoma and systemic manifestations in Japanese patients.Study Design: A retrospective observational case series.Methods: The medical records of 35 patients with tuberous sclerosis who underwent ophthalmological examination were reviewed. The retinal astrocytic hamartomas were classified into four types based on the optical coherence tomography findings, and their association with systemic disease was evaluated.Results: A total of 40 retinal astrocytic hamartomas in 13 eyes of eight patients aged 4–28 years were identified. Optical coherence tomography images were obtained for 23 lesions in 10 eyes of seven patients. Retinal astrocytic hamartomas were seen as protruding lesions of varying heights (maximum thickness, range between 221 to 1043 μm). Of the 23, 15 lesions showed homogeneous reflectivity; in six lesions, hyper-reflective spots that presumably represented intratumoral calcification were noted. Vitreous changes were noted in 13 lesions; vitreous seeding by retinal astrocytic hamartoma was observed in seven eyes. There were no significant differences in the rates of each systemic feature among the optical coherence tomography types.Conclusion: Retinal astrocytic hamartomas were classified into four types according to the previous reports; however, this classification may be worthless because the extent of protrusion did not correspond to the intratumoral characteristics, and the involved depth of the retina was not same even in the same type. An association between the type of retinal astrocytic hamartoma and systemic manifestations was not confirmed in this small case series. We considered that the classification of retinal astrocytic hamartoma and its association with systemic manifestations need further study.

To describe the first case of retinal injury by a misuse of a toy using light-emitting diode.

Time dependent change of an accumulation of an amphiphilic photosensitizer, ATX-S10(Na) on rabbit corneal neovascularization (CoNV) was evaluated by angiography using ATX-S10(Na) as a fluorescent dye on three rabbits. The angiography showed that the dye accumulated on CoNV 3–5hr after dye injection when the dye in the iris was minimum. The results suggested 3–5hr after might be the optimal time to start photodynamic therapy (PDT) to occlude CoNV selectively without damage to the surrounding normal tissue such as the iris. Then the optimal treatment parameters in PDT using ATX-S10(Na) for selective occlusion of the CoNV were investigated on rabbit eyes. PDT was performed with two different time intervals between dye injection and laser irradiation of a diode laser (670nm), different laser doses and three different dye doses on 21 animals. PDT performed immediately after dye injection selectively occluded CoNV with laser irradiations from 30.6 to 38.2Jcm−2and a 2mgkg−1dose of ATX-S10(Na), as well as with 15.3Jcm−2and a 6mgkg−1dose. PDT performed 4hr after dye injection with 107.0–152.8Jcm−2and a 6mgkg−1dose, as well as with 38.2–53.5Jcm−2and a 12mgkg−1dose was also effective. Although PDT performed either immediately or 4hr after ATX-S10(Na) injection selectively occluded CoNV, the width of the optimal range of radiant exposures seemed wider in PDT performed 4hr after dye injection. It is supposed that this result is associated with the difference of dye accumulation between in CoNV and in normal tissue as shown by the present angiographical findings.

ATX‐S10(Na), a hydrophilic chlorin photosensitizer having an absorption maximum at 670 nm, is a candidate second‐generation photosensitizer for photodynamic therapy (PDT) for cancer treatment. In this study, we examined plasma protein binding, cellular uptake and subcellular targets of ATX‐S10(Na) in vitro.Protein binding ratios of 50 μg/ml ATX‐S10(Na) in rat, dog and human plasma were 73.0%, 87.2% and 97.7%, respectively. Gel filtration chromatography revealed that 1 mg/ml ATX‐S10(Na) bound mainly to high‐density lipoprotein (HDL) and serum albumin at the protein concentration of 0.4%, with binding ratios of 46% and 36%, respectively. The free form of ATX‐S10(Na) was mostly incorporated into T.Tn cells, and its cellular uptake was partially but significantly inhibited by endocytosis inhibitors such as phenylarsine oxide, chloroquine, monensin and phenylglyoxal, and by chilling the cells to 4°C. However, ouabain, harmaline, sodium cyanide, probenecid and aspartic acid did not influence the uptake of ATX‐S10(Na), suggesting that cellular uptake of ATX‐S10(Na) was not related to sodium‐potassium pump activity, sodium‐dependent transporter activity, mitochondrial oxidative respiration, organic anion transporter activity or aspartic acid transporter activity. By fluorescence microscopy, lysosomal localization of ATX‐S10(Na) was observed in T.Tn cells. However, electron microscopic observation revealed that many subcellular organelles such as mitochondria, endoplasmic reticulum, ribosomes, Golgi complex and plasma membrane were damaged by PDT using 25 μg/ml ATX‐S10(Na) soon after laser irradiation at 50 J/cm2, and tumor necrosis was rapidly induced. This result indicated that ATX‐S10(Na) was widely distributed within the cell.

ATX‐S10(Na), a hydrophilic chlorin photosensitizer having an absorption maximum at 670 nm, is a candidate second‐generation photosensitizer for use in photodynamic therapy (PDT) for cancer treatment. The effectiveness of PDT using ATX‐S10(Na) and a diode laser for experimental tumors was evaluated in vitroand in vivo. In‐vitroPDT using ATX‐S10(Na) and the diode laser showed drug concentration‐, laser dose‐ and drug exposure time‐dependent cytotoxicity to various human and mouse tumor cell lines. In Meth‐A sarcoma‐implanted mice, optimal PDT conditions were found where tumors were completely eliminated without any toxicity. Against human tumor xenografts in nude mice, the combined use of 5 mg/kg ATX‐S10(Na) and 200 J/cm2laser irradiation 3 h after ATX‐S10(Na) administration showed excellent anti‐tumor activity, and its efficacy was almost the same as that of PDT using 20 mg/kg porfimer sodium and a 100 J/cm2excimer dye laser 48 h after porfimer sodium injection. Microscopic observation of tumor tissues revealed that PDT using ATX‐S10(Na) and the diode laser induced congestion, thrombus and degeneration of endothelial cells in tumor vessels, indicating that a vascular shutdown effect plays an important role in the anti‐tumor activity of PDT using ATX‐S10(Na) and the diode laser.

In order to elucidate the mechanism by which a new photosensitizer ATX-S10 causes the photodynamic effect on neovasculature, we investigated the kinetics and localization of dye accumulation in the neovascular cornea of rats after systemic administration and the development of vascular injury induced by subsequent laser irradiation, compared to those in the normal iris. Under a fluorescence microscope, the neovascular cornea always exhibited more intense fluorescence than the iris between 0.5 and 4 hr after ATX-S10 administration, indicating the preferential deposit of dye in the former tissue. The fluorescence was found inside the vascular lumen at the earliest time period and thereafter in the vascular lining cells, interstitial tissue and infiltrating neutrophils until 6 hr. As observed using light and electron microscopy, laser irradiation performed 2.5 hr after ATX-S10 injection caused extensive vascular thrombosis with endothelial destruction, which persisted for at least 3 days. The proportion of thrombosed vessels at 6 hr after laser irradiation in the neovascular cornea (64±5%;n=3) was significantly (P<0.01) higher than that in the normal iris (44±8%;n=3). In the non-thrombosed vessels from heparinized rats, in which thrombosis-related ischemic effect was excluded, mitochondrial vacuolation was the pathologic change commonly seen in the endothelial cells, pericytes and neutrophils. Morphometric analysis revealed that the mitochondria of endothelial cells in the corneal new vessels were more severely injured than those in the iris vessels. The present results indicate that ATX-S10 is a potent photosensitizer which induces photodynamic occlusion particularly of new vessels probably due to the preferential biodistribution of dye in the neovascular tissue.

Laser indirect ophthalmoscope (LIO) photocoagulation and transscleral photocoagulation through the conjunctiva and subconjunctiva were performed in the fundus of chinchilla gray rabbits using various exposure times and powers, and the thresholds for retinal blanching and choroidal hemorrhage were determined. The therapeutic range was described for both applications as the ratio between energy values to produce grayish white lesions and hemorrhage at 50% probability. The therapeutic range appeared to remain almost constant with different exposure times. The mean ratio with LIO was 3.2±0.28, similar to that with slit-lamp delivery reported in our previous study. The mean ratio with transscleral photocoagulation through the conjunctiva and subconjunctiva were 2.48 ± 0.28 and 2.38 ± 0.26, respectively. The variability of LIO appeared to be a little lower than with transscleral photocoagulation. There was no significant difference between the variability with transscleral photocoagulation through the conjunctiva and subconjunctiva.