Lens capsule pathological characteristics in cases of intraocular lens dislocation with atopic dermatitis.

PURPOSE: To explore lens capsule pathological characteristics in intraocular lens (IOL) dislocation after cataract surgery in patients with atopic dermatitis (AD). SETTING: University hospital department of ophthalmology. DESIGN: Case series with clinicopathological correlations. METHODS: Lens capsules and surrounding tissues excised during surgery from eyes with AD (AD group) and eyes without AD (non-AD group) with IOL dislocation were histologically evaluated. Hematoxylin and eosin staining was used to assess abnormal changes in lens epithelial cells (LECs). Masson trichrome staining distinguished the fibrous metaplasia around the lens capsule into high-density and low-density fibrosis. Capsular splitting (thinning) was identified in both stained preparations. RESULTS: The IOL dislocation morphology in the AD group (10 eyes of 10 patients) included 7 cases of capsular bag dislocation (CBD) and 3 cases of dead bag syndrome (DBS), with an average duration to IOL dislocation of 11.5 ± 5.6 years. All patients in the non-AD group (12 eyes of 12 patients) had CBD, averaging 10.2 ± 5.7 years to dislocation. Abnormal LECs, low-density fibrosis, and capsular splitting were observed in 9 (90), 9 (90), and 6 (60) of the patients in the AD group compared with 6 (50), 3 (25), and 2 (18), respectively, in the non-AD group (total n [%]). CONCLUSIONS: Compared with the non-AD group, the AD group exhibited higher frequencies of morphological changes in LECs, low-density fibrosis around the lens capsule, and capsular splitting characteristics of DBS. These results suggest LEC degeneration and increased lens capsule fragility occurred in patients with AD.

Lens thickness in atopic cataract: case-control study.

PURPOSE: To examine whether atopic cataracts are associated with thinner lenses. SETTING: Department of Ophthalmology, Jikei University Hospital, Tokyo, Japan. DESIGN: Retrospective matched case-control study. METHODS: 31 eyes with atopic cataracts, 62 with nonatopic cataracts, and 31 without cataracts were analyzed. Each group was matched for age (±4 years) and sex. RESULTS: The mean lens thickness (LT) was 3.76 ± 0.40 mm, 3.94 ± 0.49 mm, and 4.11 ± 0.40 mm in eyes with atopic cataracts, nonatopic cataracts, and normal lenses, respectively. Repeated-measures analysis of variance showed that the LT in the atopic cataract group was significantly thinner than that in the nonatopic cataract ( P = .036) and normal lens ( P < .001) groups. In multivariate logistic regression analysis, a thinner LT was negatively correlated with age (odds ratio [OR], 0.91; 95% CI, 0.86-0.96) and positively correlated with anterior subcapsular cataract (ASC) (OR, 5.61; 95% CI, 1.97-15.99). Atopy was not a significant factor. 24 (38.7%) of the 62 eyes with nonatopic cataracts and 24 (77.4%) of the 31 eyes with atopic cataracts had ASC. CONCLUSIONS: The lenses of eyes with atopic cataracts were thinner than those of controls. Atopic cataracts frequently present with anterior subcapsular opacity, which is associated with lens thinning.

Multi-Contrast Magnetic Resonance Imaging of Visual White Matter Pathways in Patients With Glaucoma.

Purpose: Glaucoma is a disorder that involves visual field loss caused by retinal ganglion cell damage. Previous diffusion magnetic resonance imaging (dMRI) studies have demonstrated that retinal ganglion cell damage affects tissues in the optic tract (OT) and optic radiation (OR). However, because previous studies have used a simple diffusion tensor model to analyze dMRI data, the microstructural interpretation of white matter tissue changes remains uncertain. In this study, we used a multi-contrast MRI approach to further clarify the type of microstructural damage that occurs in patients with glaucoma. Methods: We collected dMRI data from 17 patients with glaucoma and 30 controls using 3-tesla (3T) MRI. Using the dMRI data, we estimated three types of tissue property metrics: intracellular volume fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fraction (IsoV). Quantitative T1 (qT1) data, which may be relatively specific to myelin, were collected from all subjects. Results: In the OT, all four metrics showed significant differences between the glaucoma and control groups. In the OR, only the ICVF showed significant between-group differences. ICVF was significantly correlated with qT1 in the OR of the glaucoma group, although qT1 did not show any abnormality at the group level. Conclusions: Our results suggest that, at the group level, tissue changes in OR caused by glaucoma might be explained by axonal damage, which is reflected in the intracellular diffusion signals, rather than myelin damage. The significant correlation between ICVF and qT1 suggests that myelin damage might also occur in a smaller number of severe cases.

Surgical Technique for Pars Plana Ahmed Glaucoma Valve Implantation in Advanced Glaucoma: The Upside-Down Technique.

PRCIS: Ahmed glaucoma valve (AGV) implantation using the upside-down technique resulted in an aqueous humor outflow pathway, occurring primarily on the scleral side and secondarily on the conjunctival side, and was effective in treating refractory glaucoma. PURPOSE: To describe the AGV surgical technique, which results in changes in the primary aqueous humor outflow pathway to the scleral side (upside-down technique), and to evaluate the clinical effects and distribution of bleb fluid after surgery in patients with refractory glaucoma. PATIENTS AND METHODS: In this retrospective study, the upside-down technique was used for pars plana AGV implantation in 10 eyes of 10 patients with refractory glaucoma. Surgical success was defined by complications, intraocular pressure (IOP), the glaucoma medication score, and bleb fluid distribution determined by magnetic resonance imaging. RESULTS: Postoperatively, there were significant reductions in the IOP and medication score at 23 and 27 months, respectively (P<0.05). Although a transient hypertensive phase was observed in 7 patients, it was controlled without ocular massage and additional surgery. A patient who had suprachoroidal hemorrhage during surgery lost light perception 7 months after the surgery, and another patient developed hypotony at 3 and 4 months after surgery, which spontaneously improved during subsequent examinations. Magnetic resonance imaging showed that the double bleb layer adjacent to the endplate tended to have more bleb fluid on the conjunctival side than on the scleral side facing the outlet (n=8; 1 to 29 mo after surgery). CONCLUSIONS: Pars plana AGV implantation using the upside-down technique was a relatively effective alternative to manage inadequate IOP control in patients with refractory glaucoma.

Characteristics of Japanese patients with Leber's hereditary optic neuropathy and idebenone trial: a prospective, interventional, non-comparative study.

PURPOSE: Leber's hereditary optic neuropathy (LHON) is a mitochondrial neuropathy that causes acute vision loss. Idebenone, a short-chain ubiquinone analog that preserves mitochondrial function is thought to suppress disease progression in early-onset LHON patients. We investigated the effects of idebenone in Japanese LHON patients. STUDY DESIGN: Prospective, interventional, non-comparative study in patients with definite LHON diagnosis, under trial registration number UMIN000017939. METHODS: Fifty-seven patients received 900 mg/day idebenone for 24 weeks. We measured baseline best-corrected visual acuity, visual fields, critical fusion frequency and retinal ganglion cell layer complex thickness; we assessed efficacy at 24 and 48 weeks, and safety throughout. RESULTS: Patients were predominantly male (91.2%) and most had an mt.11778G>A mutation (94.7%). All patients tolerated idebenone therapy well. Data from the 51 mt.11778 patients were compared with their baseline data. At 48 weeks, significant improvement in best-corrected visual acuity was observed in 17 patients (33.3%). Furthermore, 25.5% of patients showed improvements in visual fields and 33.3% in critical fusion frequency. However, retinal ganglion cell layer complex thickness was significantly reduced. Among patients who started idebenone >1 year after disease onset, visual improvement was found in 12 (38.7%). Among patients who developed LHON before 19 years of age, visual improvement was found in 11 (42.3%). CONCLUSION: Idebenone's potential and favorable safety profile were confirmed in Japanese LHON patients. However, this study had no placebo group; therefore, we need to undertake a prospective intervention study to further investigate the therapeutic effects of Idebenone in Japanese LHON patients.

V1 Projection Zone Signals in Human Macular Degeneration Depend on Task Despite Absence of Visual Stimulus.

Identifying the plastic and stable components of the visual cortex after retinal loss is an important topic in visual neuroscience and neuro-ophthalmology.1-5 Humans with juvenile macular degeneration (JMD) show significant blood-oxygen-level-dependent (BOLD) responses in the primary visual area (V1) lesion projection zone (LPZ),6 despite the absence of the feedforward signals from the degenerated retina. Our previous study7 reported that V1 LPZ responds to full-field visual stimuli during the one-back task (OBT), not during passive viewing, suggesting the involvement of task-related feedback signals. Aiming to clarify whether visual inputs to the intact retina are necessary for the LPZ responses, here, we measured BOLD responses to tactile and auditory stimuli for both JMD patients and control participants with and without OBT. Participants were instructed to close their eyes during the experiment for the purpose of eliminating retinal inputs. Without OBT, no V1 responses were detected in both groups of participants. With OBT, to the contrary, both stimuli caused substantial V1 responses in JMD patients, but not controls. Furthermore, we also found that the task-dependent activity in V1 LPZ became less pronounced when JMD patients opened their eyes, suggesting that task-related feedback signals can be partially suppressed by residual feedforward signals. Modality-independent V1 LPZ responses only in the task condition suggest that V1 LPZ responses reflect task-related feedback signals rather than reorganized feedforward visual inputs.

Spontaneous Improvement of Visual Acuity in a 13-Year-Old Boy with Neuromyelitis Optica Spectrum Disorder.

Ophthalmic and MRI evaluations of a 13-year-old boy who reported loss of visual acuity in his right eye demonstrated the presence of unilateral optic neuritis. After serological tests showed positivity for anti-aquaporin 4 antibody, he was diagnosed with neuromyelitis optica spectrum disorder. Encephalopathy and myelitis were not observed. Since his unilateral optic neuritis was considered to reflect mild disease activity, only follow-up observations were performed. Visual acuity and central scotoma improved 1 week after the first examination. In the absence of any specific treatments, good visual acuity has remained for 20 months, with no relapse of optic neuritis.

Free radical production by femtosecond laser lens irradiation in porcine eyes.

PURPOSE: To investigate the relationship between the generation of free radicals and femtosecond laser lens irradiation. SETTING: AMO Laboratory, Tokyo, Japan. DESIGN: Ex vivo studies. METHODS: Hydroxyphenyl fluorescein (HPF) was injected into the anterior chamber of fresh 6-month-old porcine cadaver eyes (N = 31). After laser irradiation, a plate reader was used to measure the fluorescence of the aqueous humor samples. Relative fluorescence units (RFU) were calculated by subtracting the average control value from the measured values of all the samples. Experiment 1: After determining the RFU in the 7 laser-irradiated eyes, the relationship with the amount of laser energy was then assessed. Experiment 2: To clarify the issue regarding the degree of attenuation of the fluorescence intensity, HPF was simultaneously injected into 2 eyes, with 1 eye irradiated and the other eye used as a control. After dividing the RFU of the laser-irradiated eye by the control RFU, the laser irradiation-control RFU ratio was calculated, and the relationship with the laser irradiation energy amount then assessed. RESULTS: There was a significant correlation between the femtosecond laser lens irradiation energy and the RFU in the aqueous humor (P < .05, analysis of variance). CONCLUSIONS: Femtosecond laser lens irradiation increases the quantity of free radicals in the aqueous humor, with the extent of the increase dependent on the amount of laser energy. These results suggest that excessive laser irradiation during femtosecond laser-assisted cataract surgery might cause corneal endothelial damage because of the free radicals created during the procedure.

Diffusivity and quantitative T1 profile of human visual white matter tracts after retinal ganglion cell damage.

In patients with retinal ganglion cell diseases, recent diffusion tensor imaging (DTI) studies have revealed structural abnormalities in visual white matter tracts such as the optic tract, and optic radiation. However, the microstructural origin of these diffusivity changes is unknown as DTI metrics involve multiple biological factors and do not correlate directly with specific microstructural properties. In contrast, recent quantitative T1 (qT1) mapping methods provide tissue property measurements relatively specific to myelin volume fractions in white matter. This study aims to improve our understanding of microstructural changes in visual white matter tracts following retinal ganglion cell damage in Leber's hereditary optic neuropathy (LHON) patients by combining DTI and qT1 measurements. We collected these measurements from seven LHON patients and twenty age-matched control subjects. For all individuals, we identified the optic tract and the optic radiation using probabilistic tractography, and evaluated diffusivity and qT1 profiles along them. Both diffusivity and qT1 measurements in the optic tract differed significantly between LHON patients and controls. In the optic radiation, these changes were observed in diffusivity but were not evident in qT1 measurements. This suggests that myelin loss may not explain trans-synaptic diffusivity changes in the optic radiation as a consequence of retinal ganglion cell disease.

Influence of irrigation dynamic pressure-assisted hydrodissection on intraocular pressure and the posterior chamber-anterior hyaloid membrane barrier during cataract surgery.

PURPOSE: To evaluate the effects of irrigation dynamic pressure-assisted hydrodissection (irrigation-hydro: iH) on intraocular pressure (IOP) and the posterior chamber-anterior hyaloid membrane (PC-AHM) barrier in porcine eyes. STUDY DESIGN: Experimental. METHODS: In Experiment 1, IOP was recorded while irrigating the anterior chamber (AC), during iH, and during phacoemulsification and aspiration in 20 porcine eyes using bottle heights of 50, 70, and 90 cm. Under the same conditions, IOP was recorded during conventional manual cortical cleaving hydrodissection (manual hydro: mH) in 20 porcine eyes. In Experiment 2, after iH, ACs were perfused for 5 seconds with balanced salt solution containing 1.0-µm fluorescein beads in 20 porcine eyes using bottle heights of 70, 118, and 169 cm. PC-AHM barrier staining grade was evaluated by the Miyake-Apple view. RESULTS: iH proved successful in all cases. In Experiment 1, IOP during iH was relatively stable and peak IOP was below the baseline bottle height-dependent pressure. No eyes showed a peak IOP > 75 mmHg during iH, but 8 eyes showed a peak IOP > 75 mmHg during mH. In Experiment 2, neither AHT nor ruptured capsules were observed at any bottle height. CONCLUSION: Unlike mH, IOP during iH was relatively stable without any high peak IOP. Thus, iH offers a simple technique for reducing peak IOP and avoiding disturbance of the PC-AHM barrier.

The safety and efficacy of phaco-sleeve irrigation-assisted hydrodissection during femtosecond laser-assisted cataract surgery.

Femtosecond laser-assisted cataract surgery (FLACS) changes the intraoperative environment due to the generation of intracapsular gas that induces a high intracapsular volume. Manual hydrodissection (mH) may induce high intracapsular pressure (ICP) and additional intracapsular volume, thereby leading to capsular block syndrome (CBS). Since the phaco-sleeve irrigation-assisted hydrodissection (iH) technique is used to initially groove and split the lens and remove the intracapsular gas, this can reduce the intracapsular volume while bypassing the intracapsular lens prior to the hydrodissection. As iH uses the phaco tip to intentionally vacuum the intraocular fluid for use in inducing the irrigation jet from the sleeve side holes, the ICP cannot surpass the set irrigation pressure, thereby avoiding CBS. Using this technique, we performed FLACS without CBS in 310 cataract eyes. Our findings suggest that the iH technique may be beneficial for patients by preventing CBS during FLACS.

Age-related macular degeneration affects the optic radiation white matter projecting to locations of retinal damage.

We investigated the impact of age-related macular degeneration (AMD) on visual acuity and the visual white matter. We combined an adaptive cortical atlas and diffusion-weighted magnetic resonance imaging (dMRI) and tractography to separate optic radiation (OR) projections to different retinal eccentricities in human primary visual cortex. We exploited the known anatomical organization of the OR and clinically relevant data to segment the OR into three primary components projecting to fovea, mid- and far-periphery. We measured white matter tissue properties-fractional anisotropy, linearity, planarity, sphericity-along the aforementioned three components of the optic radiation to compare AMD patients and controls. We found differences in white matter properties specific to OR white matter fascicles projecting to primary visual cortex locations corresponding to the location of retinal damage (fovea). Additionally, we show that the magnitude of white matter properties in AMD patients' correlates with visual acuity. In sum, we demonstrate a specific relation between visual loss, anatomical location of retinal damage and white matter damage in AMD patients. Importantly, we demonstrate that these changes are so profound that can be detected using magnetic resonance imaging data with clinical resolution. The conserved mapping between retinal and white matter damage suggests that retinal neurodegeneration might be a primary cause of white matter degeneration in AMD patients. The results highlight the impact of eye disease on brain tissue, a process that may become an important target to monitor during the course of treatment.

Irrigation port hydration in phacoemulsification surgery.

BACKGROUND: In most cases, hydration is performed by water injection into the stromal tissue with a needle. The technique is simple, however it is sometimes troublesome. PURPOSE: We describe a simple technique for hydrating the corneal stroma in cataract surgery using an irrigation port. PATIENTS AND METHODS: The technique began by pushing the irrigation port against the corneal stroma for a few seconds during phacoemulsification, which generated edema in the corneal incision that subsequently prevented leakage. This procedure is called the hydration using irrigation port (HYUIP) technique. A total of 60 eyes were randomized and placed in two groups, 30 eyes underwent surgeries using the HYUIP technique (HYUIP group) and 30 eyes underwent surgeries without the HYUIP technique (control). The three points evaluated during each surgery included 1) the occurrence of anterior chamber collapse during the pulling out of the I/A tip after inserting the intraocular lens, 2) the need for conventional hydration, and 3) watertight completion at the end stage of surgery. RESULTS: The anterior chamber collapse and the need for conventional hydration were significantly smaller in the HYUIP group compared to the control group. Regarding the self-sealing completion, no significant difference was observed between the two groups. CONCLUSION: The HYUIP technique is an effective method for creating self-sealing wound. In addition, this technique helps to prevent anterior chamber collapse.

Irrigation dynamic pressure-assisted hydrodissection during cataract surgery.

The irrigation dynamic pressure-assisted hydrodissection technique (irrigation-hydro [iH]) does not require performing manual hydrodissection using a syringe and cannula to achieve cortical-capsular cleavage during cataract surgery. Since the iH technique uses the phaco tip to intentionally vacuum the intraocular fluid in order to induce the irrigation dynamic pressure for cortical-capsular cleavage, there is a reduction in the intraocular pressure (IOP) from the bottle-height-dependent hydrostatic pressure. Thus, since the peak irrigation pressure derived from the phaco tip sleeve will be limited by the height of the irrigation fluid bottle, this is advantageous in helping to avoid excessively high IOP during cortical-capsular hydrodissection. Using this technique, we were able to effectively perform phacoemulsification without complications in 607 of 609 cataract eyes. Our findings show that utilization of the iH technique would be of benefit to patients, as it prevents high-pressure hydrodissection-related complications, such as capsular block syndrome and tears in the anterior hyaloid membrane during cataract surgery.

Use of the phaco tip technique for lens cleavage and removal during cataract surgery.

Use of the phaco tip technique for lens cleavage and removal does not require manual hydrodissection using a syringe and cannula, or cortical removal using an irrigation/aspiration tip. The phaco tip is the only surgical instrument required for this technique. Its advantages include maintaining a stable intraocular pressure during cortical cleaving hydrodissection and lens removal, which includes the cortex.

Clinical and Genetic Findings of Autosomal Recessive Bestrophinopathy in Japanese Cohort.

PURPOSE: To report the clinical and genetic findings of 9 Japanese patients with autosomal recessive bestrophinopathy (ARB). DESIGN: Retrospective, multicenter observational case series. METHODS: Nine ARB patients from 7 unrelated Japanese families that were examined in 3 institutions in Japan were studied. A series of ophthalmic examinations including fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, electrooculography (EOG), electroretinography, and the results of genetic analysis were reviewed. RESULTS: Genetic analyses identified 7 pathogenic variants in BEST1 including 2 novel variants, c.478G>C (p.A160P) and c.948+1delG. Homozygous variants were found in 4 families and compound heterozygous variants were found in 3 families. Two patients were diagnosed as ARB only after the whole exome sequencing analyses. The Arden ratio of the EOG was less than 1.5 in all 7 patients tested. Vitelliform lesions typical for Best vitelliform macular dystrophy were not seen in any of the patients. Seven patients shared some of the previously described features of ARB: subretinal deposits, extensive subretinal fluid, and cystoid macular edema (CME). However, the other 2 patients with severe retinal degeneration lacked these features. Focal choroidal excavations were present bilaterally in 2 patients. One case had a marked reduction of the CME and expansion of subretinal deposits over an 8-year of follow-up period. CONCLUSIONS: Japanese ARB patients had some but not all of the previously described features. Genetic analyses are essential to diagnose ARB correctly in consequence of considerable phenotypic variations.

White matter consequences of retinal receptor and ganglion cell damage.

PURPOSE: Patients with Leber hereditary optic neuropathy (LHON) and cone-rod dystrophy (CRD) have central vision loss; but CRD damages the retinal photoreceptor layer, and LHON damages the retinal ganglion cell (RGC) layer. Using diffusion MRI, we measured how these two types of retinal damage affect the optic tract (ganglion cell axons) and optic radiation (geniculo-striate axons). METHODS: Adult onset CRD (n = 5), LHON (n = 6), and healthy controls (n = 14) participated in the study. We used probabilistic fiber tractography to identify the optic tract and the optic radiation. We compared axial and radial diffusivity at many positions along the optic tract and the optic radiation. RESULTS: In both types of patients, diffusion measures within the optic tract and the optic radiation differ from controls. The optic tract change is principally a decrease in axial diffusivity; the optic radiation change is principally an increase in radial diffusivity. CONCLUSIONS: Both photoreceptor layer (CRD) and retinal ganglion cell (LHON) retinal disease causes substantial change in the visual white matter. These changes can be measured using diffusion MRI. The diffusion changes measured in the optic tract and the optic radiation differ, suggesting that they are caused by different biological mechanisms.

Hydrodissection-free phacoemulsification surgery: mechanical cortical cleaving dissection.

UNLABELLED: We describe hydrodissection-free phacoemulsification surgery (hydro-free phaco), which eliminates conventional cortical-cleaving hydrodissection during cataract surgery. To replace hydrodissection, we devised a mechanical cortical-cleaving dissection technique that is performed during phacoemulsification. The new technique prevents the high pressure within the endocapsular space or the posterior chamber-anterior hyaloid membrane barrier area that is common with hydrodissection. This reduces hydrodissection-related complications such as posterior capsule rupture, anterior hyaloid membrane tear, extension of zonule fracture, and pseudoexpulsive hemorrhage. Using this technique, phacoemulsification was performed effectively without complications in 547 of 550 cataract eyes. We propose this technique to prevent hydrodissection-related complications in eyes with a high risk for complications. FINANCIAL DISCLOSURE: Neither author has a financial or proprietary interest in any material or method mentioned.

Plasticity and stability of the visual system in human achiasma.

The absence of the optic chiasm is an extraordinary and extreme abnormality in the nervous system. The abnormality produces highly atypical functional responses in the cortex, including overlapping hemifield representations and bilateral population receptive fields in both striate and extrastriate visual cortex. Even in the presence of these large functional abnormalities, the effect on visual perception and daily life is not easily detected. Here, we demonstrate that in two achiasmic humans the gross topography of the geniculostriate and occipital callosal connections remains largely unaltered. We conclude that visual function is preserved by reorganization of intracortical connections instead of large-scale reorganizations of the visual cortex. Thus, developmental mechanisms of local wiring within cortical maps compensate for the improper gross wiring to preserve function in human achiasma.