Non-treated Eyes Research Articles

Effects of orthokeratology and spectacle lenses with highly aspherical lenslets on unilateral myopic anisometropia control.

To evaluate the 1-year effects of orthokeratology (OK) lenses and spectacle lenses with highly aspherical lenslets (HALs) on axial length (AL) elongation in children with unilateral myopic anisometropia. This ambispective cohort study recruited 81 children aged 8-14 years with unilateral myopic anisometropia. Of these, 42 participants (mean age 11.07 ± 1.54 years; 23 males) were treated with monocular OK lenses (OK group), and 39 (mean age 10.64 ± 1.72 years; 22 males) with binocular HALs (HAL group). Changes in AL and spherical equivalent refraction (SER) from baseline at 3, 6 and 12 months were compared between eyes and groups. Kaplan-Meier estimation and Cox proportional hazard regression were performed to analyse the risk of myopia onset in the initially non-myopic eyes. Mean axial elongation in the myopic and non-myopic eyes at the 12-month follow-up visit were 0.17 ± 0.20 and 0.41 ± 0.26 mm in the OK group (p < 0.001) and 0.10 ± 0.15 and 0.12 ± 0.12 mm in the HAL group (p = 0.32), respectively. Compared with the OK group, the non-myopic eyes in the HAL group had less axial elongation, lower cumulative myopia incidence and percentage of participants with rapid myopic shift at the 6- and 12 month follow-up (all p < 0.05). Cox regression analysis showed that a higher initial SER decreased the risk of myopia onset significantly in the initially non-myopic eyes (B = -2.06; 95% CI, 0.03-0.49; p = 0.003). Monocular OK lenses suppressed axial elongation in the myopic eye and minimised anisometropia; however, the non-treated contralateral eye may experience faster myopia onset and myopic shift. Binocular HALs can effectively reduce axial elongation in both eyes of children with unilateral myopic anisometropia.

Phase 1 Study of JNJ-81201887 Gene Therapy in Geographic Atrophy Secondary to Age-Related Macular Degeneration

ObjectiveTo evaluate the safety and tolerability of a single intravitreal injection of JNJ-81201887 (JNJ-1887) in patients with geographic atrophy (GA) secondary to advanced dry age-related macular degeneration (AMD). DesignPhase 1, open-label, single-center, first-in-human clinical study. SubjectsAdult patients (aged ≥50 years) with GA secondary to AMD in the study-treated eye (treated eye) with a best corrected visual acuity (BCVA) Snellen equivalent of 20/200 or worse in the treated eye (20/80 or worse after the first 3 patients), a total GA lesion size between 5 and 20 mm2 (2-8 disc area), and BCVA of 20/800 or better in fellow, non-treated eye were included. MethodsPatients (N=17) were sequentially enrolled into low (3.56×1010 viral genome [vg]/eye; n=3), intermediate (1.07×1011 vg/eye; n=3), and high (3.56×1011 vg/eye; n=11) dose cohorts without steroid prophylaxis and assessed for safety and tolerability over 24 months. Main Outcome MeasuresSafety and tolerability outcomes included assessment of ocular and non-ocular treatment-emergent adverse events (AEs) over 24 months. Secondary outcomes included GA lesion size and growth rate. ResultsBaseline patient characteristics were consistent with the disease under study, and all enrolled patients had foveal center–involved GA. JNJ-1887 was well tolerated across all cohorts, with no dose-limiting AEs. There were no serious or systemic AEs related to study intervention. Overall, 5/17 (29%) patients experienced 6 events of mild ocular inflammation related to study treatment; exam findings in all resolved, and AEs resolved in 4 of 5 patients following topical steroids or observation. One unresolved vitritis event, managed with observation, occurred in a patient with an unrelated fatal AE. No endophthalmitis or new-onset choroidal neovascularization was reported. GA lesion growth rate was similar among all cohorts over 24 months. For treated eyes in the high-dose cohort, GA lesion growth rate showed continued decline through 24 months, with a reduction in mean square root lesion growth from 0.211 mm at months 0-6 to 0.056 mm at months 18-24. ConclusionsAll 3 studied doses of JNJ-1887 had a manageable safety profile through 24 months of follow-up. Further investigation of JNJ-1887 for the treatment of GA is warranted.

Using 2% PVPI topical solution for serial intravitreous injections and ocular surface findings: a case control study

BackgroundThe use of povidone-iodine for ocular surface asepsis is widespread for intravitreal injections. They became frequent procedures, leading to serial exposure of patients’ eyes to iodinated solutions. In this study, we investigate the changes in the ocular surface in patients submitted to repeated use of povidine for intravitreal injection of anti-VEGF asepsis, analyzing Ocular Surface Disease Index, non-invasive break up time, blinking quality, lipid layer, meniscus height and osmolarity.MethodsThis case-control study included 34 individuals (68 eyes), 14 males, 20 females aged 48 to 94. Inclusion criteria were individuals who received application of 2% povidone-iodine eyedrops for intravitreal injections treatment with the non-treated contralateral eye used as control. Ocular surface examinations were performed at a single occasion. A pre-intravitreal injection asepsis protocol with povidone-iodine was applied. All statistical analysis was performed using the STATA® 18.0 Software and a p-value = 0.05 was considered as the statistical significance value in all tests.ResultsThe median number of IVIs in treated eyes was 12 (range 6–20). The results in treated eyes compared with untreated eyes were respectively : median OSDI 16 (IQR 6–39) and 12.5 (IQR 8–39) (p = 0.380); mean NIBUT 10.30 (SD ± 2.62) and 10.78 (SD ± 2.92) ( s, p = 0.476); median blinking quality 100 (IQR 100) and 100 (IQR 100 ) (%, p = 0.188); median lipid layer 87 (IQR 77–90) and 86 (IQR 74–100) (nm, p = 0.451); median meniscus height 0.22 (IQR 0.19-0,31) and 0.24 (IQR 0.20–0.27) (mm, p = 0.862), median Meibomian gland atrophy 33 (IQR 24–45) and 31.5 (IQR 25–39) (%, p = 0.524); and mean osmolarity 306.6 (SD ± 21.13) and 313.8 (SD ± 29) (mOsm, p = 0.297). There was no statistically significant relationship between the repetitive use of 2% iodinated solution and signs or symptoms compatible with dry eye syndrome in this group of patients.ConclusionsThe findings suggest that 2% povidone iodine is a safe and efficacious agent for ocular surface antisepsis during intravitreal injections, not leading to substantial ocular surface modifications. This conclusion supports the continued use of povidone iodine in routine ophthalmic procedures without increased risk of inducing dry eye syndrome.

Effect of Long-Acting Diquafosol Sodium on Astigmatism Measurement Repeatability in Preoperative Cataract Cases with Dry Eyes: A Multicenter Prospective Study.

Dry eye can compromise corneal astigmatism measurement repeatability during preoperative cataract surgery examination. No previous studies have analyzed the effectiveness of long-acting 3% diquafosol sodium (LA-DQS) on astigmatism measurement repeatability. This research assessed the effect of LA-DQS on astigmatism measurement repeatability in preoperative patients with cataract and short tear break-up time (TBUT) type dry eyes in both eyes of the same patient. Correlations between repeatability and TBUT, corneal high-order aberrations (HOAs), and corneal astigmatism magnitude were also analyzed. In total, 122 eyes (61 patients) with short TBUT-type dry eye were enrolled. Preoperatively, only one eye of all patients was treated with LA-DQS for 4 weeks. TBUT and corneal HOAs were checked using CASIA 2 before and 4 weeks post-treatment. The cylindrical power and meridian of astigmatism were measured at 3- and 4-week post-treatment using IOLMaster 700. Power vectors J0 and J45 were used for astigmatism calculations. Repeatability of astigmatism measurements was assessed as the within-subject standard deviation (Sw). The relative effects of TBUT and HOAs on J0 Sw and J45 Sw were also analyzed. Comparative changes in these variables were evaluated between treated and non-treated eyes, with additional analysis of their correlations. Treated eyes exhibited significant improvements in TBUT, HOAs, and post-treatment measurements of J0 Sw and J45 Sw at 3 and 4 weeks. In non-treated eyes, J0 Sw and J45 Sw showed significant correlation with TBUT and corneal HOAs. HOAs showed stronger relative associations with J0 Sw and J45 Sw than TBUT. In non-treated eyes, no significant correlation was found between cylindrical power and astigmatism measurement repeatability. In short TBUT-type dry eye, preoperative treatment with LA-DQS significantly improved astigmatism measurement repeatability. This may improve the precision of intraocular lens (IOL) power calculations regardless of the magnitude of corneal astigmatism, especially when toric IOLs are used.

OCT risk factors for 2-year foveal involvement in non-treated eyes with extrafoveal geographic atrophy and AMD

PurposeTo assess the relationship of optical coherence tomography (OCT) findings and progression to foveal atrophy in a cohort of eyes with extrafoveal geographic atrophy (GA) and age-related macular degeneration (AMD) at inclusion.MethodsWe retrospectively analyzed 45 participants (45 eyes) with extrafoveal GA at baseline and with 2 years of regular follow-ups. Several OCT qualitative features (i.e., presence of foveal flat pigment epithelium detachment with a thin double layer sign [DLS] and reticular pseudodrusen, GA focality) and quantitative measurements (outer retinal layer thickness, retinal pigment epithelium [RPE] to Bruch’s membrane [BM] volume, minimum distance from the central foveal circle, and untransformed GA lesion size area) were assessed at baseline. Logistic regression analyses were carried out to identify independent significant predictors and compute odds ratios (ORs) for the risk of the development of atrophy.ResultsAt month 24, 26 eyes (57.8%) developed atrophy in the foveal central circle, while 11 eyes (24.4%) developed atrophy in the foveal central point. Significant independent predictive features for the development of atrophy in the foveal central circle included foveal outer retinal thickness (OR, 0.867; p = 0.015), minimum distance from the foveal central circle (OR, 0.992; p = 0.022), and foveal thin DLS (OR, 0.044; p = 0.036). The only independent predictive feature for the development of atrophy in the foveal central point was the presence of foveal thin DLS (OR, 0.138; p = 0.017).ConclusionsWe identified OCT risk factors for 2-year foveal atrophy in eyes with untreated extrafoveal GA at baseline.

Staphyloma-induced Serous Maculopathy: Natural Course and Treatment Effects

To study the natural course of staphyloma-induced serous maculopathy (SISM) and the effects of treatments. Retrospective case series. This retrospective analysis included 26 eyes of 20 patients with SISM and at least 12 months of follow-up. Medical records were reviewed for patient demographics, such as age, sex, spherical equivalent, best-corrected visual acuity (BCVA), type of staphyloma, and imaging characteristics. Spectralis OCT B-scans were evaluated for the presence and height of the serous retinal detachment (SRD) at each follow-up visit. An SRD episode was defined as a period with SRD in 1 patient. Changes in SRD height and BCVA. Twenty-six eyes of 20 patients (70% female) were included. The mean age was 54 ± 11 years, and the mean spherical equivalent was -4.8 ± 3.3 diopters at baseline. The staphyloma was located inferior in 12 eyes (46%), inferonasal in 7 eyes (27%), and nasal in 7 eyes (27%). The mean follow-up duration was 73 ± 34 months. During follow-up, the SRD height fluctuated in all eyes, with a mean change of 125 ± 56 μm. The SRD disappeared completely during follow-up in 13 eyes (50%) and then reappeared in 7 eyes (35%). Resolution occurred spontaneous in 8 eyes (31%). The median time of an SRD episode was 25 (interquartile range 14-57) months. Treatment was performed in 20 eyes (77%) and led to resolution of SRD in 3 of the 15 photodynamic therapy treatments (21%), 2 of 5 (40%) anti-VEGF series, and 2 of 4 eyes (50%) treated with topical prednisolone. Best-corrected visual acuity at the final visit (0.42 ± 0.25) was not significantly different from BCVA at baseline (0.34 ± 0.27 logarithm of the minimum angle of resolution, P= 0.07), nor was BCVA change significantly different between treated eyes (n= 19) and nontreated eyes (n= 7, P= 0.3). Serous retinal detachment in patients with SISM fluctuated over time and resolved without treatment in 31% of the eyes. Because treatment does not change the course of BCVA, a wait-and-see policy is advocated in these patients on the exclusion of treatable causes of SRD. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Turnover of Microaneurysms After Intravitreal Injections of Faricimab for Diabetic Macular Edema.

Microaneurysm (MA) plays an important role in the pathogenesis of diabetic macular edema (DME) progression and response to anti-vascular endothelial growth factor (VEGF) therapy. This study aimed to investigate the effect of faricimab, a bispecific antibody against angiopoietin-2 and VEGF, on the number of MAs and their turnover in the treatment of DME. We included that patients with DME who underwent three monthly injections of faricimab in one eye, with the other eye as control. We examined central retinal thickness (CRT) based on optical coherence tomography (OCT) and best-corrected visual acuity. Turnover, including loss and newly formed MAs, and the total number of MAs were counted based on merged images of the OCT map and fluorescein angiography. We enrolled 28 patients with DME. After 3 monthly injections of faricimab, CRT significantly improved, 66.0 ± 16.2% of MAs disappeared, and 6.71 ± 5.6% of new MAs were generated, resulting in total reduction to 40.7 ± 15.2%. In the treated eyes, MA disappearance (P < 0.0001) and turnover (P = 0.007) were significantly greater, and new formation was smaller (P < 0.0001) than in non-treated eyes. The size of the retained MAs decreased after treatment. Microaneurysm turnover was not significantly different between areas with and without edema before treatment. In the process of improving edema in DME with faricimab, MAs shrink and disappear, and formation of MAs are inhibited, resulting in decreased total number of MAs. Intravitreal administration of faricimab suppresses vascular permeability and improves vascular structure.

Single Center Experience with Voretigene Neparvovec Gene Augmentation Therapy in RPE65 Mutation–Associated Inherited Retinal Degeneration in a Clinical Setting

To assess the impact of baseline data on psychophysical and morphological outcomes of subretinal voretigene neparvovec (VN) (Luxturna, Spark Therapeutics, Inc.) treatment. Single-center, retrospective, longitudinal, consecutive case series. Patients with RPE65-biallelic mutation-associated inherited retinal degeneration (RPE65-IRD) treated between February 2020 and March 2022 with VN and oral immunosuppression according to the manufacturer's recommendation by one surgeon (F.G.H.). Retrospective analysis of surgical and clinical records, ancillary testing, and retinal imaging after VN therapy for RPE65-IRD. Descriptive statistics compared data at baseline up to 32 months post-treatment. Best-corrected visual acuity (BCVA), low-luminance VA (LLVA), Goldmann visual fields (GVFs), chromatic full-field stimulus threshold (FST) testing (FST), scotopic and photopic 2-color threshold perimetry (2CTP), and multimodal retinal imaging. Thirty eyes of 19 patients were analyzed (10 pediatric patients < 20 years; 20 adult patients > 20 years of age; overall range: 8-40 years) with a median follow-up of 15 months (range, 1-32). The fovea was completely or partially detached in 16 eyes, attached in 12 eyes, and not assessable in 2 eyes on intraoperative imaging. Median BCVA at baseline was better in the pediatric group (P < 0.05) and did not change significantly independent of age. Meaningful loss of BCVA (≥ 0.3 logarithm of the minimal angle of resolution [logMAR]) occurred in 5 of 18 adult eyes, and a meaningful gain (≥-0.3 logMAR) occurred in 2 of 18 adult and 2 of 8 pediatric eyes. The LLVA and scotopic 2CTP improved considerably in pediatric patients. Scotopic blue FST improved at all ages but more in pediatric patients (8/8 eyes gained ≥ 10 decibels [dB]; P < 0.05). In pediatric patients, median GVF improved by 20% for target V4e and by 50% for target III4e (target I4e not detected). Novel atrophy developed in 13 of 26 eyes at the site of the bleb or peripheral of vascular arcades. Improvements in FST did not correlate with development of chorioretinal atrophy at 12 months. Mean central retinal thickness was 165.87 μm (± 26.26) at baseline (30 eyes) and 157.69 μm (± 30.3) at 12 months (26 eyes). Eight adult patients were treated unilaterally. The untreated eyes did not show meaningful changes during follow-up. These data in a clinical setting show the effectiveness of VN therapy with stable median BCVA and mean retinal thickness and improvements of LLVA, FST, and 2CTP up to 32 months. Treatment effects were superior in the pediatric group. We observed new chorioretinal atrophy in 50% of the treated eyes. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Efficacy of Topical 0.05% Cyclosporine A for Ocular Surface Disease Related to Topical Anti-Glaucoma Medications.

Purpose: We aimed to determine the therapeutic efficacy of 0.05% topical cyclosporine A (CsA) for chronic ocular surface disease (OSD) in patients using benzalkonium chloride (BAK)-preserved antiglaucoma eye drops. Methods: A prospective, randomized, paired-eye, controlled clinical trial was conducted with participants who had been instilling at least one BAK-preserved topical antiglaucoma drug in both eyes for at least 6 months. Topical CsA was only applied in randomly selected unilateral eyes. Visual field (VF) indices, ocular surface parameters, tear meniscus height (TMH), and matrix metalloproteinase-9 (MMP-9) immunoassay were evaluated at baseline and at 2 and 4 months. Results: Seventy eyes from 35 participants were included in the study. The Schirmer I, tear breakup time, and TMH increased by 4.5 ± 8.6 mm (P < 0.01), 5.0 ± 5.3 s (P < 0.001), and 85.4 ± 159.0 μm (P < 0.01) in the treated eyes at 4 months from baseline, respectively. The ocular staining score and MMP-9 positivity in the treated eyes decreased by 2.2 ± 1.3 (P < 0.001) and 0.7 ± 0.9 points (P < 0.001), respectively, at 4 months. In untreated eyes, only TMH increased by 41.4 ± 92.1 μm (P = 0.016) from baseline to 4 months. In VF indices, the tracking failure frequency was 19.09% ± 21.62%, and the test duration was 336.0 ± 79.5 s in the treated eyes at 4 months, which were lower than 34.37% ± 23.13% (P < 0.001) and 375.9 ± 70.7 s (P < 0.05) in the nontreated eyes. Conclusion: Application of topical 0.05% CsA significantly improved the OSD parameters and the reliability indices of VF tests. This study was registered with the Clinical Research Information Service (CRIS) (number KCT0007124).

AAV-mediated expression of HLA-G for the prevention of experimental ocular graft vs. host disease

Ocular graft versus host disease (OGvHD) develops after allogeneic hematopoietic stem cell transplantation (HSCT) and manifests as ocular surface inflammatory disease. This study evaluated the efficacy of adeno-associated virus (AAV) gene therapy encoding human leukocyte antigen G (HLA-G) to inhibit OGvHD. A major histocompatibility mismatch chronic OGvHD murine model was evaluated. 7days after HSCT, mice were dosed subconjunctivally with scAAV8-HLA-G1/5 (1 x 109 vg/eye), topical cyclosporine (twice daily), or left untreated. Body weights and tear production (red thread test) were recorded, and eyelid, corneal opacity, and corneal fluorescein retention were scored through day 44 after HSCT. Tissues were collected for vector biodistribution, ocular histology, and immunofluorescence. Compared with untreated HSCT eyes, those dosed with scAAV8-HLA-G1/5 had significantly reduced clinical inflammatory signs of OGvHD. On histology, eyes that received scAAV8-HLA-G1/5 or cyclosporine had a significantly lower mean limbal mononuclear cell count when compared with non-treated HSCT eyes. HLA-G immunofluorescence was detected in the subconjunctiva and peripheral cornea in HSCT animals treated with scAAV8-HLA-G1/5. Vector genomes were detected in the lacrimal gland, but not in the other tested organs. These results provide evidence that subconjunctival AAV targets ocular surface and corneal disease and support that HLA-G-based gene therapy may be an effective treatment for OGvHD.

Neuroprotective effect of the calcium channel blocker nilvadipine on retinal ganglion cell death in a mouse ocular hypertension model

We investigated whether nilvadipine has a neuroprotective effect on retinal ganglion cells (RGCs) in a mouse model of ocular hypertension (OH) that expresses cyan fluorescein protein (CFP) in RGCs. OH was induced in the right eyes of Thy1-CFP transgenic mice using a laser. Nilvadipine or vehicle treatment began simultaneously with OH modeling and was administered intraperitoneally once daily for 8 weeks. Intraocular pressure (IOP) in both the laser- and non-treated eyes was measured weekly with the microneedle method, and calculations were performed to estimate the pressure insult in each eye. Using a retinal whole mount, the number of RGCs was counted at week 9. Laser-treated eyes showed a significant increase in IOP (p < 0.01), and the pressure insult did not differ between the drug-treated groups. Over time, laser treatment produced a significant decrease in the number of RGCs in the vehicle-treated groups, but this effect was attenuated by nilvadipine treatment. The pressure insult and RGC survival rate were significantly negatively correlated in the vehicle-treated group (y = -0.078 x + 107.8, r = 0.76, p < 0.001), but not in the nilvadipine-treated group (y = -0.015 x + 99.9, r = 0.43, p = 0.128). Nilvadipine was a potent neuroprotective agent for RGCs in our mouse model of OH and may have potential for protection against glaucoma. This model is useful as a screening tool for drugs with retinal protective effects.

Associations between Serial Intravitreal Injections and Dry Eye

To investigate the effects of serial intravitreal injections (IVI) on the ocular surface and meibomian glands (MG) in patients treated with anti-vascular endothelial growth factor (anti-VEGF) for neovascular age-related macular degeneration (nAMD). Retrospective controlled observational study. Patients with nAMD receiving unilateral IVI with anti-VEGF agents. The fellow eye was used as control. Tear film and ocular surface examinations were performed on a single occasion at a minimum of four weeks after IVI. A pre-IVI asepsis protocol with povidone-iodine was applied. Upper and lower MG loss, tear meniscus height (TMH), bulbar redness score (BR), non-invasive tear break-up time (NIBUT), tear film osmolarity (TOsm), Schirmer test, corneal staining, fluorescein tear film break-up time (TBUT), meibomian gland expressibility (ME) and meibum quality (MQ). Ninety patients with a mean age of 77.5 years (SD 8.4; range 54-95) were included. The median number of IVI in treated eyes was 19.5 (range 2-132). Mean MG loss in the upper eyelid was 19.1 (SD 11.3) % in treated eyes and 25.5 (SD 14.6) % in untreated fellow eyes (P=0.001). For the lower eyelid, median MG loss was 17.4 (IQR 9.4-29.9) % in treated eyes and 24.5 (IQR 14.2-35.2) % in fellow eyes (P<0.001). Mean BR was 1.32 (SD 0.46) in treated eyes versus 1.44 (SD 0.45) in fellow eyes (P=0.017). Median TMH was 0.36 (IQR 0.28-0.52) mm in treated eyes and 0.32 (IQR 0.24-0.49) mm in fellow eyes (P=0.02). There were no differences between treated and fellow eyes regarding NIBUT, TOsm, Schirmer test, corneal staining, fluorescein TBUT, meibomian gland expressibility ME or MQ. Repeated IVI with anti-VEGF with preoperative povidone-iodine application was associated with reduced meibomian gland loss, increased tear volume and reduced signs of inflammation compared to fellow non-treated eyes in patients with nAMD. This regimen may thus have a beneficial effect on the ocular surface.

Refractive outcomes following unilateral laser treatment for type 1 retinopathy of prematurity

To compare refractive outcomes of infants with type 1 retinopathy of prematurity (ROP) in whom one eye was treated with laser and the fellow eye spontaneously regressed. The medical records of infants who underwent IVB and laser treatment for type 1 ROP or aggressive posterior-ROP between January 2016 and December 2019 were retrospectively evaluated. Infants in whom ROP in the fellow eye regressed and for whom refractive data was available in the record were included in the study. Refractive outcomes of unilaterally treated infants were assessed. A total of 283 cases were reviewed: of these, 17 experienced spontaneous regression in the fellow eye and were included. All unilateral laser-treated eyes had type 1 ROP in zone Ⅱ. The median age at treatment was 40 weeks' postmenstrual age (IQR, 39-41). The mean spherical equivalent at the last examination was 2.1 ± 2.5 D in treated eyes and 2.50±1.4 D in nontreated eyes, at a mean age of 25.0 ± 9.1 months (P = 0.378). Ofthe 7 infants who underwent fluorescein angiography, the median of the ratio of the length of the temporal retinal vascularization to the optic disk-to-fovea distance was 3.71 (3.22-3.79) in treated and 4.28 (3.90-4.49) in untreated eyes, at a median age of 18 months (P = 0.018). In laser-treated eyes with peripheral zone Ⅱ ROP and with advanced treatment age, wedidnot observe a significant myopic change compared to the fellow untreated eye.

Evaluation of a novel combination of TRAM-34 and ascorbic acid for the treatment of corneal fibrosis in vivo.

Corneal injury and aberrant wound healing commonly result in corneal fibrosis and subsequent vision loss. Intermediate-conductance calmodulin/calcium-activated K+ channels (KCa3.1) have been shown to promote fibrosis in non-ocular and ocular tissues via upregulation of transforming growth factor beta (TGFβ). TRAM-34 is a selective inhibitor of KCa3.1 and reduces fibrosis by downregulation of TGFβ-induced transdifferentiation of stromal fibroblasts to myofibroblasts. Ascorbic acid has been demonstrated to be effective in promoting corneal re-epithelialization and reduction of neovascularization via anti-VEGF and anti-MMP mechanisms. This study evaluates tolerability and efficacy of a novel combination of TRAM-34 (25μM) and ascorbic acid (10%) topical treatment for corneal fibrosis using an established in vivo rabbit model and conducting clinical eye examinations. Markers of corneal fibrosis were evaluated in all corneas at study endpoint via histopathology, immunofluorescence, and quantitative real-time PCR. The eyedrop treated eyes showed significantly improved clinical outcomes based on modified McDonald Shadduck scores, reduction of clinical haze on Fantes scores, and reduction of central corneal thickness (CCT). At cellular and molecular levels, eyedrop treatment also significantly reduced expression of alpha smooth muscle actin (α-SMA) mRNA and protein, collagen III mRNA, and fibronectin mRNA compared to non-treated eyes. Our study suggests that a tested new bimodal eyedrop is well tolerated and effectively reduces corneal fibrosis/haze in rabbits in vivo.

Inter-eye comparison of retinal vascular growth rate and angiographic findings following unilateral bevacizumab treatment.

To compare retinal vascularization progression rate, final retinal vascularization, and fluorescein angiography (FA) findings in infants who received intravitreal bevacizumab (IVB) treatment in one eye and with spontaneous regression in the other eye. Thirty eyes of 15 infants who underwent IVB in one eye due to asymmetric retinopathy of prematurity, and who had pre-treatment fundus photographs and fluorescein angiography images were included in the study. Horizontal disc diameter (DD), optic disc-to-fovea distance (FD), and the length of temporal retinal vascularization (LTRV) distance were measured by evaluating pre-treatment and FA images. The mean ages at the time of treatment and FA were 40.38 ± 3.35 and 68.72 ± 10.52 weeks postmenstrual age, respectively. The pre-treatment LTRV/FD ratio was 3.11 ± 0.41 in the treated eyes and 3.26 ± 0.43 in the non-treated eyes (p = 0.053). The final LTRV/FD ratio was 4.23 ± 0.38 in the treated group and 4.33 ± 0.37 in the non-treated group (p = 0.286). Staining of the vessels, hyperfluorescent focus, and irregular branching of the vessels were similar between the groups, respectively (p = 1.000; p = 0.250; p = 0.625). The progression rate of retinal vascularization and angiographic findings were similar between the treated eyes and the non-treated eyes. Our study suggests that incomplete retinal vascularization in eyes treated with anti-vascular endothelial growth factor (VEGF) is due to the nature of the disease, and anti-VEGF treatment was not to cause cessation in vascular progression.

Changes in choroidal vascular structure from vitreoretinal lymphoma and the intraocular cytokine level associated with clinical resolution after intravitreal methotrexate treatment.

PurposeTo evaluate changes in choroidal vascular structure and aqueous cytokine levels in eyes with vitreoretinal lymphoma (VRL) after intravitreal methotrexate (MTX) treatment.MethodsIn this retrospective study, VRL patients who visited our hospital between October 2018 and July 2020 were reviewed. Aqueous samples were obtained before treatment and at clinical resolution after intravitreal MTX therapy. Interleukin (IL)-6 and IL-10 levels and the IL-10-to-IL-6 ratio were evaluated. Swept-source optical coherence tomographic images were obtained along with the aqueous samples. Subfoveal choroidal thickness (SFCT), total vascular area of the choroid (TCA), stromal area (SA), luminal area (LA), and choroidal vascularity index (CVI) were assessed.ResultsTwelve patients were enrolled (female:male—5:7). The mean age (± standard deviation) at diagnosis was 60.9±8.5 years. In the 16 eyes diagnosed with VRL, values of SFCT, TCA, LA, and SA significantly decreased after treatment (all p-values <0.05). Additionally, the aqueous cytokine IL-10 level and IL-10-to-IL-6 ratio were significantly decreased (p = 0.001 and p = 0.003, respectively). The choroidal structure in the non-treated fellow eyes did not show any significant difference. There were no further changes in SFCT, TCA, LA, or CVI that occurred during maintenance therapy. For clinical remission, the patients received 7.7±5.5 intravitreal MTX injections. The required number of injections for clinical remission was positively correlated with best-corrected visual acuity, IL-10, and IL-6 levels in the active phase (p = 0.035, p = 0.009, and p = 0.031, respectively).ConclusionEyes with active VRL exhibited choroidal thickening with increased vascular and stromal areas that decreased after remission following MTX treatment. Higher aqueous IL-10 and IL-6 levels and lower visual acuity in the active phase may indicate the number of injections required for remission; this should be considered in the treatment of patients with VRL.

Oral Scutellarin Treatment Ameliorates Retinal Thinning and Visual Deficits in Experimental Glaucoma.

Purpose: Intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma, yet glaucoma can continue to progress despite controlled IOP. Thus, development of glaucoma neurotherapeutics remains an unmet need. Scutellarin is a flavonoid that can exert neuroprotective effects in the eye and brain. Here, we investigated the neurobehavioral effects of scutellarin treatment in a chronic IOP elevation model.Methods: Ten adult C57BL/6J mice were unilaterally injected with an optically clear hydrogel into the anterior chamber to obstruct aqueous outflow and induce chronic IOP elevation. Eight other mice received unilateral intracameral injection of phosphate-buffered saline only. Another eight mice with hydrogel-induced unilateral chronic IOP elevation also received daily oral gavage of 300 mg/kg scutellarin. Tonometry, optical coherence tomography, and optokinetics were performed longitudinally for 4 weeks to monitor the IOP, retinal nerve fiber layer thickness, total retinal thickness, visual acuity, and contrast sensitivity of both eyes in all three groups.Results: Intracameral hydrogel injection resulted in unilateral chronic IOP elevation with no significant inter-eye IOP difference between scutellarin treatment and untreated groups. Upon scutellarin treatment, the hydrogel-injected eyes showed less retinal thinning and reduced visual behavioral deficits when compared to the untreated, hydrogel-injected eyes. No significant difference in retinal thickness or optokinetic measures was found in the contralateral, non-treated eyes over time or between all groups.Conclusion: Using the non-invasive measuring platform, oral scutellarin treatment appeared to preserve retinal structure and visual function upon chronic IOP elevation in mice. Scutellarin may be a novel neurotherapeutic agent for glaucoma treatment.

Delayed follow-up of medical retina patients due to COVID-19: impact on disease activity and visual acuity.

PurposeThe coronavirus pandemic has prompted unprecedented delays to treatment with anti-VEGF intravitreal injections due to the need to reduce hospital attendances and prioritise the patients at highest risk of vision loss. This study aims to quantify the effect of these delays on visual acuity (VA) outcomes and optical coherence tomography (OCT) features for patients receiving treatment for neovascular age-related macular degeneration (nAMD), retinal vein occlusions (RVO) and diabetic macular oedema (DMO) and correlate to the Royal College of Ophthalmologists guidelines (RCOphth).MethodsA retrospective data analysis of an electronic medical record was performed on a random sample of eyes receiving anti-VEGF injections for nAMD, RVO or DMO. Data collected included age, sex, reason for injection, number of weeks delay if > 8 weeks from that planned, VA at baseline and follow-up and the OCT features, if delayed. For those eyes not delayed, a visual acuity at 20 weeks was recorded to provide a control group.ResultsA sample of 981 eyes (858 patients) were analysed. There was a delay in review of 8 weeks or more in 39.6% of patients of which 30.4% had since returned for review (28.4% nAMD, 37.6% RVO and 30.0% DMO). There was no demographic difference identified between the delayed and non-delayed patients; however, the delayed group was significantly more likely to have better vision in their non-treated eye (p = 0.0003). A statistically significant difference was found in the change in VA between the delayed and the not-delayed group for eyes with nAMD (p = 0.001) but not for RVO or DMO. For the delayed group, mean CMT increased by 33 and 100 μm, respectively, for nAMD and RVO and decreased by 7.8 μm for DMO. The VA of 89.7% of DMO eyes returned to baseline, compared to 74.6% and 76.9% of nAMD and RVO eyes.ConclusionThe RCOphth guidance to prioritise intravitreal injections for nAMD over DMO appears appropriate in this cohort but not for RVO. Eyes with nAMD experienced the greatest loss of vision with treatment delay, and nAMD and RVO eyes were less likely to return to baseline on restarting treatment.

Effect of Laser-assisted Subepithelial Keratectomy with Mitomycin C on Corneal Optical Density Measured with Confocal Microscopy.

The development of confocal microscopy allows one to obtain high-resolution corneal images like its optical density. Some studies have evaluated the optical density with Scheimpflug cameras in the early post-operative period after photorefractive keratectomy, but no studies have evaluated the long-term evolution of optical density after surface ablation when mitomycin C is used. This work aimed to study the changes in corneal optical density measured with confocal microscopy in eyes treated with laser-assisted subepithelial keratectomy (LASEK) and intraoperative mitomycin C (MMC) to correct myopia. A study of 24 consecutive myopic eyes that underwent LASEK with 0.02% MMC and a control group of 24 healthy nontreated eyes was performed. Optical density was measured using the images by the confocal microscopy of the Heidelberg Retina Tomograph II with the Rostock Cornea Module. An analysis of confocal microscopy images was performed using the ImageJ software to obtain the optical density, in gray-scale units (GSU). The optical density of the stromal bed was evaluated 3 months, 15 months, and 3 years after surgery and was compared with the optical density at the equivalent depth of the stroma in controls. The mean values of optical density for the LASEK group were 81.7 ± 9.7, 78.6 ± 11.7, and 73.6 ± 18.7 GSU at 3 months, 15 months, and 3 years, respectively, and it was 61.8 ± 8.2 GSU for the control group. A statistically higher optical density 3 and 15 months after LASEK with MMC was found compared with controls (P < .001). No significant difference was found in optical density at 3 years post-operatively. Our study suggests that, after LASEK with MMC, the anterior corneal stroma has a higher optical density at 3 and 15 months post-operatively, which gradually returns to normal values 3 years after surgery.

Novel Short-Chain Quinones to Treat Vision Loss in a Rat Model of Diabetic Retinopathy.

Diabetic retinopathy (DR), one of the leading causes of blindness, is mainly diagnosed based on the vascular pathology of the disease. Current treatment options largely focus on this aspect with mostly insufficient therapeutic long-term efficacy. Mounting evidence implicates mitochondrial dysfunction and oxidative stress in the central etiology of DR. Consequently, drug candidates that aim at normalizing mitochondrial function could be an attractive therapeutic approach. This study compared the mitoprotective compounds, idebenone and elamipretide, side-by-side against two novel short-chain quinones (SCQs) in a rat model of DR. The model effectively mimicked type 2 diabetes over 21 weeks. During this period, visual acuity was monitored by measuring optokinetic response (OKR). Vision loss occurred 5–8 weeks after the onset of hyperglycemia. After 10 weeks of hyperglycemia, visual function was reduced by 65%. From this point, the right eyes of the animals were topically treated once daily with the test compounds. The left, untreated eye served as an internal control. Only three weeks of topical treatment significantly restored vision from 35% to 58–80%, while visual acuity of the non-treated eyes continued to deteriorate. Interestingly, the two novel SCQs restored visual acuity better than idebenone or elamipretide. This was also reflected by protection of retinal pathology against oxidative damage, retinal ganglion cell loss, reactive gliosis, vascular leakage, and retinal thinning. Overall, mitoprotective and, in particular, SCQ-based compounds have the potential to be developed into effective and fast-acting drug candidates against DR.