Choroidal vessel density in unilateral hyperopic amblyopia using en-face optical coherence tomography.

BACKGROUND: Structural changes of the choroid, such as choroidal thickening, have been indicated in amblyopic eyes with hyperopic anisometropia as compared to fellow or healthy eyes. The purpose of the present study was to investigate choroidal vascular density (CVD) in children with unilateral hyperopic amblyopia. METHODS: This study included 88 eyes of 44 patients with unilateral amblyopia due to hyperopic anisometropia with or without strabismus and 29 eyes of 29 age-matched normal controls. The CVD of Haller's layer was quantified from en-face images constructed by 3-dimensional swept-source optical coherence tomography images flattened relative to Bruch's membrane. The analysis area was a 3 × 3-mm square of macula after magnification correction. Relationships between CVD and other parameters [best-corrected visual acuity (BCVA), refractive error and subfoveal choroidal thickness (SFCT)] were investigated, and CVDs were compared between amblyopic, fellow, and normal control eyes. RESULTS: Mean CVD was 59.11 ± 0.66% in amblyopic eyes, 59.23 ± 0.81% in fellow eyes, and 59.29 ± 0.74% in normal control eyes. CVD showed a significant positive relationship with SFCT (p = 0.004), but no relationships with other parameters. No significant differences in CVD were evident among amblyopic, fellow, and normal control eyes after adjusting for SFCT (p = 0.502). CONCLUSIONS: CVD was unrelated to BCVA, and CVD did not differ significantly among amblyopic, fellow and normal control eyes. These results suggest that the local CVD of Haller's layer is unaffected in unilateral hyperopic amblyopic eyes.

Evaluation of Significance Maps and the Analysis of the Longitudinal Time Course of the Macular Ganglion Cell Complex Thicknesses in Acquired Occipital Homonymous Hemianopia Using Spectral-domain Optical Coherence Tomography.

The present study was performed to evaluate the ganglion cell complex (GCC) thickness as well as the significance map and analyse the time course of the change in GCC thickness in patients with homonymous hemianopia due to posterior cerebral artery (PCA) territory stroke using spectral-domain optical coherence tomography. This study included 40 control subjects and 11 patients with unilateral PCA territory stroke. The GCC parameters were quantified using a custom-built software programme. The GCC data, centred on the macula, was divided vertically into hemianopic and unaffected sides. GCC parameters were calculated using an average of those from both eyes. The relationship between the GCC parameters and the time after stroke was determined by regression analyses. The GCC parameters in the hemi-retinae corresponding to the affected hemifields significantly differed between the hemianopes and the control group. The area under the receiver operating characteristics curve of the GCC significance map areas was significantly high. A regression analysis revealed a significant relationship between the time after stroke and both the GCC significance map areas (r = 0.791, p = .004) and GCC thickness (r = -0.736, p = .010) on the hemianopic side. The GCC parameters on the hemianopic side were reduced in patients with acquired occipital homonymous hemianopia, and the reduction was slowly progressive probably due to transsynaptic retrograde degeneration of the retinal ganglion cells. A significance map analysis provides additional OCT parameters that could be used to investigate the effect of retrogeniculate lesions on the inner retina of patients.

Foveal avascular zone and macular vessel density after correction for magnification error in unilateral amblyopia using optical coherence tomography angiography.

BACKGROUND: To investigate the area of foveal avascular zone (FAZ) and macular vessel density (VD) after correction for magnification error in unilateral amblyopia using optical coherence tomography angiography (OCTA). METHODS: Participants comprised 15 patients with unilateral amblyopia due to anisometropia with or without strabismus (mean age, 9.8 ± 3.4 years; range, 6-17 years). OCTA images were obtained by using spectral-domain OCT with angiography software. The OCTA scanning protocol used was 3 × 3-mm volume scan centered on the fovea. OCTA images were corrected for magnification errors using individual axial length (AL), and an adjusted 2.3 × 2.3-mm square was derived as a region of interest. The FAZ area and VD in both superficial capillary plexus (SCP) and deep capillary plexus (DCP) layers, foveal minimum thickness (FMT) were assessed using built-in OCTA software and ImageJ software (NIH, Bethesda, MD). RESULTS: LogMAR in the amblyopic eyes was significantly poorer than that of the fellow eye (p < 0.001). AL was significantly shorter in the amblyopic eye than in the fellow eye (p < 0.001). FAZ area of SCP in amblyopic eyes was significantly smaller than that of fellow eyes (p < 0.001). No significant differences were seen in FAZ area of DCP, VD of SCP, VD of DCP, and FMT between amblyopic and fellow eyes (p = 0.07, 0.43, 0.55, and 0.25, respectively). CONCLUSIONS: Our present study after magnification error correction found smaller FAZ area of SCP in the amblyopic eye compared with the fellow eyes, but there was no significant difference in the macular VD between the amblyopic and fellow eyes.

Retinal Nerve Fiber Layer and Peripapillary Capillary Density Reduction Detected Using Optical Coherence Tomography Enface Images and Angiography in Optic Tract Syndrome.

In a patient with an optic tract syndrome, we describe the loss of retinal nerve fiber layer and retinal microvasculature using enface and optical coherence tomography angiography image analyses.

Effect of amblyopia treatment on choroidal thickness in hypermetropic anisometropic amblyopia using swept-source optical coherence tomography.

BACKGROUND: Recent studies using optical coherence tomography (OCT) have indicated that choroidal thickness (CT) in the anisometropic amblyopic eye is thicker than that of the fellow and normal control eyes. However, it has not yet been established as to how amblyopia affects the choroid thickening. The purpose of the present study was to investigate the effect of amblyopia treatment on macular CT in eyes with anisometropic amblyopia using swept-source OCT. METHODS: Thirteen patients (mean age: 6.2 ± 2.4 years) with hypermetropic anisometropic amblyopia were included in this study. Visual acuity (VA), axial length (AL), and CT were measured at the enrollment visit and at the final visit, after at least 6 months of treatment. CT measurements were corrected for magnification error and were automatically analyzed using built-in software and divided into three macular regions (subfoveal choroidal thickness (SFCT), center 1 mm, and center 6 mm). A one-way analysis of covariance using AL as a covariate was performed to determine whether CT in amblyopic eyes changed after amblyopia treatment. RESULTS: The average observation period was 22.2 ± 11.0 months. After treatment, VA (logMAR) improvement in the amblyopic eyes was 0.41 ± 0.19 (p < 0.001). SFCT, center 1 mm CT, and center 6 mm CT were significantly thicker in the amblyopic eyes compared with the fellow eyes both before and after treatment (p < 0.05 for all comparisons). There were no significant changes in SFCT, center 1 mm CT, or center 6 mm CT before and after treatment in the amblyopic (p = 0.25, 0.21, and 0.84, respectively) and fellow (p = 0.75, 0.84, and 0.91, respectively) eyes. The correlation between changes in logMAR versus changes in CT after treatment was not significant. CONCLUSIONS: Although VA in amblyopic eyes was significantly improved after treatment, the choroid thickening of anisometropic amblyopic eyes persisted, and there was no significant change found in the CT after the treatment. Our findings suggest that thickening of the CT in amblyopia is not directly related to visual dysfunction.

Relative Afferent Pupillary Defects in Homonymous Visual Field Defects Caused by Stroke of the Occipital Lobe Using Pupillometer.

Relative afferent pupillary defects (RAPD) may be detected in patients with occipital lobe lesions. However, no previous report has used an objective technique to record the abnormal pupillary light reflex in such cases. Therefore, we measured the pupillary light reflex objectively in 15 patients with homonymous visual field defects (HVFD) due to occipital stroke using a new pupillometer. This study detected significantly smaller and slower pupillary light reflexes in the contralateral eyes than in the other eyes, which is equivalent to the presence of RAPD in patients with HVFDs caused by retrogeniculate lesions using an objective technique. Our results confirmed those of the previous reports using the swinging flashlight test more objectively.

Macular retinal and choroidal thickness in unilateral amblyopia using swept-source optical coherence tomography.

BACKGROUND: To investigate macular retinal and choroidal thickness in amblyopic eyes compared to that in fellow and normal eyes using swept-source optical coherence tomography (SS-OCT). METHODS: This study examined 31 patients with hyperopic anisometropic amblyopia (6.9 ± 3.8 years, mean ± standard deviation), 15 patients with strabismic amblyopia without anisometropia (7.9 ± 4.2 years), and 24 age-matched controls (7.8 ± 3.3 years). Retinal and choroidal thickness was measured by 3D scans using SS-OCT. A 6-mm area around the fovea was automatically analyzed using the Early Treatment Diabetic Retinopathy Study map. The thickness from SS-OCT was corrected for magnification error using individual axial length, spherical refraction, cylinder refraction, and corneal radius. Retinal thickness was divided into the macular retinal nerve fiber layer (mRNFL), ganglion cell layer + inner plexiform layer (GCL+IPL), ganglion cell complex (GCC), and the inner limiting membrane to the retinal pigment epithelium (ILM-RPE) thickness. Retinal and choroidal thickness was compared among amblyopic, fellow, and normal eyes. RESULTS: In both amblyopia groups, there was no significant difference in the mRNFL, GCL+IPL, and GCC thicknesses among the amblyopic, fellow, and control eyes. In the anisometropic amblyopia group, choroidal thickness (subfovea, center 1 mm, nasal and inferior of the inner ring, nasal of the outer ring, and center 6 mm) of amblyopic eyes were significantly greater than that of fellow and normal eyes. In contrast, none of the choroidal thicknesses were significantly different among the investigated eyes in the strabismic amblyopia group. CONCLUSIONS: We found no significant difference in inner retinal thickness in patients with unilateral amblyopia. Although there were significant differences in choroidal thickness with hyperopic anisometropic amblyopia, there was no significant difference for the strabismic amblyopia. The discrepancy in choroidal thickness between the two types of amblyopia may be due to both differences in ocular size and underlying mechanism.

Sectoral analysis of the retinal nerve fiber layer thinning and its association with visual field loss in homonymous hemianopia caused by post-geniculate lesions using spectral-domain optical coherence tomography.

PURPOSE: To report a sectoral analysis of circumpapillary retinal nerve fiber layer (cpRNFL) thinning and its association with visual field loss using spectral-domain optical coherence tomography (SD-OCT) in patients with homonymous hemianopia following acquired post-geniculate visual pathway damage. PATIENTS AND METHODS: Seven patients with homonymous hemianopia due to unilateral acquired post-geniculate visual pathway lesions were studied. The average duration from the onset of brain lesions to the initial visit was 49.8 months. Forty-nine normal control subjects without visual field defects, as confirmed using a Humphrey visual field analyzer, were also enrolled. Measurement of the cpRNFL thickness was performed at the initial visit and 24 months using SD-OCT (RTVue-100® OCT). The cpRNFL thickness was divided into eight sectors (superior temporal: ST, temporal upper: TU, temporal lower: TI, inferior temporal: IT, inferior nasal: IN, nasal lower: NL, nasal upper: NU, superior nasal: SN). The eye on the same side as the occipital lobe lesions was defined as the ipsilateral eye, and the eye on the opposite side was defined as the contralateral eye. RESULTS: The average cpRNFL thickness in the homonymous hemianopic eyes was significantly reduced as compared with that seen in the normal controls, except for the ipsilateral eyes at the initial visit. Four of the eight sectors of the cpRNFL thickness in the homonymous hemianopic eyes were significantly reduced compared with that noted in the normal controls. In the ipsilateral eyes, the cpRNFL thickness in the ST, TU, TL, and IT sectors was significantly reduced at both the initial visit and 24 months. In the contralateral eyes, the cpRNFL thickness in the TU, TL, IT, and SN sectors was significantly reduced at both the initial visit and 24 months. The reduction of the quadrantic cpRNFL thickness significantly correlated with some of the visual field parameters, in accordance with the structure-function relationship. In the contralateral eyes, the T and I quadrant cpRNFL thickness correlated with the mean deviation and hemianopic field total deviation at 24 months. In the ipsilateral eyes, the S, T, and I quadrant cpRNFL thickness correlated with mean deviation. However, there were no correlations between the cpRNFL thickness and visual field parameters at the initial visit. CONCLUSIONS: A reduction of the cpRNFL thickness corresponding to the hemianopic visual field loss due to acquired post-geniculate visual pathway lesions was detected using SD-OCT, and the change was more evident at 24 months than at the initial visit. The latter finding suggests that this change is, at least partially, caused by transsynaptic retrograde degeneration.

Time Course of Macular and Peripapillary Inner Retinal Thickness in Non-arteritic Anterior Ischaemic Optic Neuropathy Using Spectral-Domain Optical Coherence Tomography.

To report a time course of the ganglion cell complex (GCC) and circumpapillary retinal nerve fibre layer (cpRNFL) thicknesses using spectral-domain optical coherence tomography in patients with non-arteritic anterior ischaemic optic neuropathy (NAION), five patients with unilateral NAION were studied (the average age of 66.8 ± 7.8 years old). Forty-one age-matched normal controls were also enrolled. The GCC and cpRNFL thicknesses were measured at the initial visit and at 1, 3, 6, and 12 months using RTVue-100. The GCC thickness and the cpRNFL thickness of the patients were compared with those of the normal controls. The GCC thickness in the NAION patients was 96.49 µm at the initial visit, 84.28 µm at 1 month, 74.26 µm at 3 months, 71.23 µm at 6 months, and 69.51 µm at 12 months. The values at 1, 3, 6, and 12 months were significantly reduced (p < 0.01). The cpRNFL thickness at the initial visit was significantly increased, whereas the values at 6 and 12 months were significantly reduced (p < 0.01). The GCC thickness is more useful for the detection of retinal ganglion cell loss at an early stage than the cpRNFL thickness, because the GCC thickness is unaffected by optic disc swelling at the initial visit, unlike the cpRNFL thickness.

[The influence of sodium hyaluronate solution and artificial tears on higher-order aberrations].

PURPOSE: To investigate the influence of sodium hyaluronate solution (HA) and artificial tears (AT) on higher-order aberrations (HOAs). SUBJECTS AND METHODS: Twenty four eyes of 24 normal subjects and 11 eyes of 11 dry eye patients were examined. Cornea and ocular wavefront aberrations (total, spherical-like and coma-like) were measured with a Hartmann-Shack wavefront aberrometer before and after 0.1% or 0.3% HA, AT. The consecutively obtained data of the cornea and ocular HOAs were analyzed in the central 4-mm diameter for coma-like, spherical-like and total HOAs. Average HOAs, as well as fluctuation index (FI) and stability index (SI) of the HOAs over time were compared between the two groups. RESULTS: In normal subjects, the AVE of all aberration parameters and FI showed an increase depending on viscosity of the HA (p < 0.001). After AT and 0.1% HA treatment the cornea aberration of the dry eye patients changed from a sawtooth pattern to a stable pattern. CONCLUSION: Cornea HOAs decreased, and the optical characteristics showed improvement after AT and 0.1% HA in the dry eye patients. HOAs increased depending on the viscosity of the HA, and optical stability worsened.

[Two cases of optic neuritis in children with rapid thinning of the ganglion cell complex].

BACKGROUND: There are many reports regarding the circumpapillary retinal nerve fiber layer (cpRNFL) in optic neuritis (ON). However, few studies of changes over time in the ganglion cell complex (GCC) have been reported. As far as we know, no studies of such changes in children have been reported. In the present study, we report two patients with pediatric ON in which the time course of GCC and cpRNFL were observed using optical coherence tomography. CASES: Two cases, one 9-year-old boy and one 11-year-old boy. The two patients showed acute visual impairment, relative afferent pupillary defect, and swelling of the optic disc, leading to the diagnosis of ON. Regardless of whether visual function was improved after steroid pulse therapy, thinning of the GCC and cpRNFL progressed rapidly over time. CONCLUSION: Atrophy of the retinal inner layer in the macula occurred soon after the onset of ON. Although the inflammation was reduced after treatment, atrophy of the ganglion cells continuted to progress. GCC thickness measurement in pediatric ON is useful for pathological assessment and followup, because we can detect atrophy of the ganglion cells and retinal nerve fibers soon after onset.

Changes in Choroidal Thickness and Structure Induced by 1% Atropine Instillation in Children With Hyperopic Anisometropic Amblyopia.

PURPOSE: To investigate the effects of 1% atropine eye drops on the choroidal thickness and structure of amblyopic and fellow eyes in children with hyperopic anisometropic amblyopia. METHODS: This study included 16 children with hypermetropic anisometropic amblyopia. All patients received 1% atropine eye drops in both eyes twice a day for 7 days. In the subfoveal choroidal region, choroidal thickness, total choroidal area, luminal area, and stromal area were measured quantitatively using swept-source optical coherence tomography. The choroidal parameters of the amblyopic and fellow eyes were compared between the baseline and atropine conditions. RESULTS: There were no significant differences in all choroidal parameters of the amblyopic eye between baseline and atropine conditions. However, the subfoveal choroidal thickness in the fellow eye was significantly higher for the atropine condition than the baseline condition. This change was accompanied by a significant increase in both the luminal and stromal areas of the choroid. The median differences of subfoveal choroidal thickness between the conditions were larger for the fellow eye (6.46%) than the amblyopic eye (0.26%). CONCLUSIONS: The choroidal structural change induced by 1% atropine instillation was smaller for the amblyopic eye than the fellow eye in children with hyperopic anisometropic amblyopia. Mechanisms of choroidal thickness changes could be inhibited in amblyopic eyes. [J Pediatr Ophthalmol Strabismus. 2023;60(1):39-45.].

Upper Eyelid Meibomian Gland Dysfunction is a Risk Factor for Dry Eye Symptoms Following Cataract Surgery in the Early Phase.

PURPOSE: To evaluate perioperative dry eye (DE) syndrome and meibomian gland (MG) dysfunction parameters associated with cataract surgery-induced DE symptoms. PATIENTS AND METHODS: This retrospective, single-centered, observational study included 82 eyes of 43 patients without previous subjective DE symptoms, treatment, ocular comorbidities, and previous use of ophthalmic treatment, except for anti-allergic eye drops, who underwent uncomplicated cataract surgery. MG dropout, lid margin abnormality, meibum quality, meibum expressibility, MG orifice obstruction, ocular surface disease index, non-invasive tear break-up time, tear meniscus height, and Schirmer test score were measured at baseline and 1 month postoperatively. Multivariable logistic regression with generalized estimating equation models was used to determine the risk factors for cataract surgery-induced DE symptoms. RESULTS: Twenty-one patients had subjective DE symptoms 1 month following the cataract surgery. Preoperative and postoperative parameters, preoperative upper eyelid MG loss, and female sex (odds ratio [OR] 6.72, P = 0.012; OR 4.20, P = 0.037, respectively) were identified as risk factors for cataract surgery-induced DE symptoms. CONCLUSION: Ocular parameters, including upper eyelid MG findings at baseline, were considered important in predicting persistent DE symptoms following cataract surgery.

Photopic negative response recorded with RETeval system in eyes with optic nerve disorders.

Electroretinography (ERG) is used to evaluate the physiological status of the retina and optic nerve. The purpose of this study was to determine the usefulness of ERGs recorded with the RETeval system in diagnosing optic nerve diseases. Forty-eight patients with optic nerve disorders, including optic neuritis, ischemic optic neuropathy, traumatic optic neuropathy, and dominant optic atrophy, and 36 normal control subjects were studied. The amplitudes of the photopic negative response (PhNR) were recorded with the RETeval system without mydriasis. The circumpapillary retinal nerve fiber layer thickness (cpRNFLT) was determined by optical coherence tomography (OCT). The significance of the correlations between the PhNR and cpRNFLT parameters were determined, and the receiver operating curve (ROC) analyses were performed for the PhNR and cpRNFLT. Patients with optic nerve disorders had significantly smaller PhNRs compared to the control subjects (P = 0.001). The ROC analyses indicated that both PhNR and cpRNFLT had comparable diagnostic abilities of detecting optic nerve disorders with PhNR at 0.857 and cpRNFLT at 0.764. The PhNR components recorded with the RETeval system have comparable diagnostic abilities as the cpRNFLT in diagnosing optic nerve disorders.

[Evaluation of recovery process of photoreceptor outer segment after retinal detachment repair].

PURPOSE: To evaluate the relations in the recovery process between the photoreceptor outer segment and visual acuity of repaired macula-off rhegmatogenous retinal detachment (RRD), using spectral-domain optical coherence tomography (SD-OCT). SUBJECTS AND METHODS: Twenty-three eyes with repaired macula-off RRD were examined to assess the photoreceptor inner and outer segment junctions (IS/OS), the external limiting membranes (ELM) and the thickness of the outer nuclear layer (ONL). The correlation between this recovery process and log MAR visual acuity was assessed at three months and six months after surgery. RESULTS: The mean logMAR visual acuity of the group with IS/OS disruptions at three months and without IS/OS disruptions at six months was 0.34 +/-0.09 (mean +/- SE, n=7) at three months and significantly improved to 0.06 +/- 0.08 at six months. In the group with IS/OS disruptions and without ELM disruptions at three months, the mean logMAR visual acuity was 0.36 +/- 0.27 (n=6) at three months and improved significantly to 0.07 +/- 0.24 at six months. CONCLUSIONS: There was a correlation between the reduction of visual acuity with repaired macula-off RRD and the disruption of IS/OS, and a correlation was also found between the improvement in visual acuity after repaired macula-off rhegmatogenous retinal detachment and reduction of IS/OS disruptions. The results suggest that absence of ELM disruptions is a requirement for improvement of IS/ OS disruptions.

The ROCK Inhibitor Ripasudil Shows an Endothelial Protective Effect in Patients With Low Corneal Endothelial Cell Density After Cataract Surgery.

Purpose: In the field of regenerative medicine, Rho kinase inhibitors (ROCK inhibitors) show a protective effect on the corneal endothelium and promote effective healing in acute surgical wounds. In this study, we investigated the effectiveness of eyedrops containing ripasudil, a ROCK inhibitor approved in Japan for therapeutic use for glaucoma. Methods: In this retrospective observational study, 13 glaucoma patients (16 eyes) were treated with 0.4% ripasudil eyedrops twice a day after cataract surgery. The control group comprised 13 patients (17 eyes). The averaged corneal endothelial cell density from one central and four paracentral points was <1500/mm2 (range, 527 to 1439/mm2). Results: The mean rate of increase in the thinnest corneal thickness one week after surgery was 1.25% in the ripasudil group, which was significantly lower than the 5.97% increase observed in the control group (P = 0.0037). The mean endothelial cell density loss 90 to 120 days after surgery, excluding bullous keratopathy patients for whom measurements were not possible was -4.5% in the ripasudil group, which was significantly lower than in control group (14.1%; P = 0.0003). Conclusions: The results suggest that ripasudil may help maintain corneal endothelial functional integrity and reduce cell loss after cataract surgery in patients with low corneal endothelial cell density, suggesting that it may be more broadly useful for protection of the corneal endothelium after intraocular surgery. Translational Relevance: The clinically approved ROCK inhibitor ripasudil formulated as an eye drop for glaucoma has a corneal endothelial protective effect in cataract surgery for patients with low corneal endothelial cell density.

Role of the Water Gradient Structure in Inhibiting Thin Aqueous Layer Break in Silicone Hydrogel-Soft Contact Lens.

Purpose: Soft contact lenses (SCLs) are effective for refractive error correction, but prolonged wear triggers discomfort and discontinuation. This study investigates whether water gradient technology of delefilcon A-based SCLs improve tear film dynamics. Methods: This retrospective observational study included 50 asymptomatic delefilcon A or narafilcon A users. Data on thin aqueous layer break (TALB; %), noninvasive tear break-up time (NIBUT), tear meniscus height (TMH; mm), subjective dryness, and higher-order aberrations (HOAs) were collected. Measurements of the bare eye, the SCL-worn eye after 15 minutes (visit 1 [v1]) and 30 ± 5 days after v1 after SCL was worn for ≥5 hours (visit 2 [v2]) were recorded. Results: TALB was significantly reduced in the delefilcon A group compared to the narafilcon A group (33.3% vs. 85.5% at v1; P < 0.0001 and 31.7% vs. 80.4% at v2; P < 0.0001). The NIBUT was also significantly higher in the former (4.2 ± 2.1 seconds vs. 2.9 ± 1.5 at v1; P < 0.01 and 4.1 ± 2.3 seconds vs. 2.7 ± 1.6 seconds at v2; P < 0.01) across both visits. The TMH was significantly reduced in the former in both v1 and v2. The total ocular HOAs were significantly lower in the former at v1 (P < 0.001) and v2 (P < 0.05) compared to the bare eye. Conclusions: The water gradient technology of delefilcon A reduces TALB and increases NIBUT. Translational Relevance: The use of water gradient technology improves tear film dynamics and alleviate pathological break-up pattern, improving lens performance.

Clinical Characteristics of Neovascular Age-Related Macular Degeneration without Typical Drusen.

PURPOSE: To evaluate the clinical characteristics of neovascular age-related macular degeneration (nAMD) patients without typical drusen. METHODS: We retrospectively studied 165 eyes in 165 patients with treatment-naïve nAMD, including typical AMD and polypoidal choroidal vasculopathy (PCV). According to the fellow eye condition, the patients were divided into nAMD with and without typical drusen groups. Eyes with soft drusen or subretinal drusenoid deposits were classified into the nAMD with the typical drusen group. Smoking status and diagnoses of hypertension and diabetes were identified from hospital records and patient recall. We assessed best-corrected visual acuity (BCVA), central retinal thickness (CRT) at the fovea, subfoveal choroidal thickness (SFCT), and the number of injections received. RESULTS: The nAMD without typical drusen group was significantly younger (77.9 ± 7.6 vs. 71.8 ± 8.3, P < 0.001) and had thicker SFCT at baseline (207.9 ± 99.5 vs. 260.1 ± 113.2 µm, P=0.007) and a higher proportion of PCV (30.6 vs. 63.1%, P < 0.001). The proportion of ever-smokers was significantly higher in the nAMD without typical drusen group (54.8 vs. 70.9%, P=0.036). There were no statistically significant differences in the proportion of patients with hypertension or diabetes; BCVA, CRT, or SFCT changes; or the number of injections between the nAMD with and without typical drusen groups. CONCLUSION: The clinical features of patients in the nAMD without typical drusen group were almost identical to those of pachychoroid-driven choroidal neovascularization (CNV) patients. The nAMD without typical drusen group had a significantly higher proportion of ever-smokers than the nAMD with typical drusen group. Smoking could be a risk factor for the development of pachychoroid-driven CNV.

Evaluation of Retinal Pigment Epithelial Cell Cytotoxicity of Recombinant Tissue Plasminogen Activator Using Human-Induced Pluripotent Stem Cells.

PURPOSE: The evaluation of drug-induced cytotoxicity is of great importance for the clinical application of pharmaceutical products, and human-induced pluripotent stem cells (hiPSCs) have received considerable scrutiny as a cell source for in vitro cytotoxicity testing. The aim of this study is to validate the concept of cytotoxicity testing using hiPSC-derived retinal pigment epithelium (hiPSC-RPE) by comparing the responsiveness of human fetal RPE (hfRPE) and human RPE cell line (ARPE19) to recombinant tissue plasminogen activator (rtPA). METHODS: HfRPE, two types of hiPSC-RPE, and ARPE19 were cultured in media with or without rtPA. A lactate dehydrogenase release assay was performed to investigate the dose- and time-dependent effects of rtPA on cell death. RPE function was evaluated by measuring the secretion of pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) and RPE-specific gene expression. RESULTS: Rates of cell damage in hfRPE and both hiPS-RPE were increased by rtPA supplementation (2000 and 4000 µg/ml) for 1 hour, whereas ARPE19 cell damage was increased by supplementation with rtPA at concentrations higher than 50 µg/ml. Although 100 µg/ml rtPA for 24 hours did not affect RPE cell function, sustained rtPA exposure induced prolonged cytotoxic effects in hfRPE and two hiPSC-RPE, but not ARPE19. CONCLUSION: The responsiveness of hiPSC-RPE to rtPA is similar to that of hfRPE in terms of cell death and cell function. Thus, hiPSC-RPE is a valuable cell source for in vitro cytotoxicity testing.

ROCK Inhibitor-Induced Promotion of Retinal Pigment Epithelial Cell Motility during Wound Healing.

PURPOSE: No standard therapy for RPE tear, a complication of neovascular age-related macular degeneration, exists even though RPE tears cause severe vision loss, and promotion of cell proliferation and/or migration could be a candidate RPE tear therapy. The aim of this study is to evaluate the effect of Rho-associated coiled-coil containing kinase (ROCK) inhibitor Y27632 on retinal pigment epithelial (RPE) cell motility during wound healing. METHODS: Human RPE cells were cultured in media with and without 10 µM Y27632. A luminescent cell viability assay and vinculin immunocytochemistry were used to test the Y27632 effect on RPE cell adhesion. The mean size of vinculin puncta was quantified from immunofluorescence images. RPE cell motility during wound healing was evaluated using time-lapse imaging and measuring cell migration distances and cell coverage rate in wound fields. RESULTS: The number of adhered RPE and mean size of vinculin puncta were, respectively, 20519 cells and 3.65 µm2 under nontreatment and 23569 cells and 0.66 µm2 under Y27632 treatment. Cell migration distance and cell coverage percentage for untreated and Y27632-treated cells were 98.9 and 59.4% and 203.4 and 92.5%, respectively. CONCLUSIONS: Inhibition of ROCK signaling by using 10 µM Y27632 promoted RPE cell motility during wound healing by reducing RPE cell adhesion strength.