Journal of Ophthalmic and Vision Research (JOVR)

Editorial – Application of Nanoscopic Quantum Systems in Retinal Restoration

Hadi Mohammadi, Hashem Rafii-Tabar — Sun, 10 Mar 2024 00:00:00 +0000

This is an Editorial and does not have an abstract. Please download the PDF or view the article in HTML.

Editorial – Polymeric Nanoparticles for Retinal Drug Delivery

Mazda Rad-Malekshahi — Sun, 10 Mar 2024 00:00:00 +0000

This is an Editorial and does not have an abstract. Please download the PDF or view the article in HTML.

Full Thickness Prophylactic Scleral Windows Decrease the Rate of Choroidal Effusion and Drainage Surgery after Ahmed Glaucoma Valve Implantation

Afsoon Baghbanmanesh, Masoumeh Sadat Masoumpour, Reza Razeghinejad — Sun, 10 Mar 2024 00:00:00 +0000

Purpose: To evaluate the effect of creating a full-thickness prophylactic scleral window (PSW) during Ahmed glaucoma valve (AGV) surgery on the rate of postoperative choroidal effusion and choroidal drainage surgery.

Methods: In this retrospective matched case-control study, after insertion of AGV tube a PSW was created in one group. The control-matched group had AGV without a PSW. Primary outcome measures were the rate of choroidal effusion formation and choroidal drainage surgery.

Results: In total, 544 patients (604 eyes) had undergone AGV implantation from 2013 to 2017. The PSW group consisted of 111 eyes of 111 patients and the control group had 111 eyes of 98 matched patients. There were no differences for systemic diseases, number of anti-glaucoma drugs, aspirin use, smoking, laterality of the operated eye, axial length, and central corneal thickness between the groups. Out of 12 eyes with choroidal effusion, only one belonged to the PSW group (P=0.02). Six eyes in the control group needed choroidal drainage surgery, but none of the eyes in the PSW group required this procedure (P=0.02). No intra- and postoperative issues were observed at the site of the scleral window in the PSW group.

Conclusion: PSW creation during AGV surgery is a safe method to decrease the rate of choroidal
effusion and choroidal drainage surgery

Fluorescein versus Indocyanine Green Angiography Guided Half-Dose Photodynamic Therapy for Chronic Central Serous Chorioretinopathy

Sun, 10 Mar 2024 00:00:00 +0000

Purpose: To compare the outcomes of fluorescein angiography (FA)-guided and indocyanine green angiography (ICGA)-guided half-dose photodynamic therapy (PDT) in patients with chronic central serous chorioretinopathy (CSC).

Methods: In this retrospective comparative study, medical records of eyes with chronic CSC who underwent half-dose PDT were reviewed. A retina specialist performed FA-guided half-dose PDT, and the other performed ICGA-guided treatment. The success of applying PDT in the resolution of subretinal fluid was compared between the FA- and ICGA-guided methods.

Results: Eighty-two eyes of 73 patients (41 eyes in each group) received half-dose PDT. After half-dose PDT, a significant improvement in the best-corrected visual acuity (BCVA) was found at the time of the last follow-up in both groups (both P < 0.001), with no significant intergroup difference. Central subfield and subfoveal choroidal thicknesses decreased significantly in both groups at the last follow-up (all P < 0.05), with no significant differences between the groups. Subretinal fluid (SRF) resolved in all eyes, and no persistent SRF was detected during the follow-up period.

Conclusion: FA-guided and ICG-guided half-dose PDT may have similar efficacy for the treatment of chronic CSC.

Dark Adaptometry and Optical Coherence Tomography-Angiography in Huntington Disease

Aaditya Shah, Spencer Fuller, Susan Criswell, Rajendra Apte — Sun, 10 Mar 2024 00:00:00 +0000

Purpose: Huntington’s Disease (HD) is a fully penetrant neurodegenerative disease leading to cognitive and motor disturbances. The retina may serve as a structural and functional extension of the central nervous system to identify biomarkers of HD using noninvasive imaging technology such as optical coherence tomography angiography (OCTA) and dark adaptometry.

Methods: This case–control study included 12 HD participants (24 eyes) recruited from the Huntington’s Disease Society of America Center of Excellence at Washington University in St. Louis along with 16 control participants (31 eyes). Disease-positive participants underwent imaging testing of retinal capillary density and foveal avascular zone utilizing OCTA along with dark adaptometry testing. Data were collected from November 2020 to February 2022.

Results: Individuals with HD had a lower mean age-adjusted superficial foveal capillary density and a higher mean deep foveal capillary density compared to control subjects. There was no significant difference in the mean foveal avascular zone or in dark adaptometry testing between the two groups.

Conclusion: This study suggests that changes in retinal biomarkers may exist in patients with HD and that additional investigations using multimodal techniques are warranted.

Short-Term Effects of Adding Topical Ketorolac to Intravitreal Bevacizumab in Diabetic Macular Edema: A Crossover Randomized Clinical Trial

Sun, 10 Mar 2024 00:00:00 +0000

Purpose: To evaluate the short-term additive effects of topical ketorolac to intravitreal bevacizumab (IVB) in the management of center-involved diabetic macular edema (CI-DME).

Methods: In a randomized double-masked placebo-controlled crossover clinical trial, eyes with CI-DME and the best-corrected visual acuity (BCVA) between (20/40) and (20/400) were included. These eyes should have had at least one intravitreal anti-VEGF injection in the preceding two months. They were randomized into two groups; while both groups received two IVB injections with a six-week interval, one group received topical ketorolac every 6 hr in the first interval and artificial tears every 6 hr as a placebo in the second interval and the other group received the same medications using a crossover method. The main outcome measures were changes in BCVA and central macular thickness (CMT) .

Results: Fifty-seven eyes of 35 patients with CI-DME were included in the study. The mean BCVA improvement was –0.09 ± 0.47 logMAR in the periods of receiving ketorolac and –0.03 ± 0.12 logMAR in the periods of placebo treatment, respectively (P = 0.99). Corresponding changes in CMT were –13.1 ± 170.1 and +11.7 ± 157.7 µm in the ketorolac and placebo periods, respectively (P = 0.322). The treatment effect was not statistically significant regarding both BCVA and CMT changes. Statistical analysis also disclosed that the carryover effect was insignificant for BCVA and CMT. Although the period effect was not significant for BCVA, it was at a meaningful level for CMT changes (P = 0.012).

Conclusion: This crossover clinical trial demonstrated that in the course of DME treatment with IVB injections, topical ketorolac did not have any additive beneficial effect at least during a six-week period.

Andrographis Paniculata (Burm. F.) Flavonoid Compound and Prevention of Diabetic Retinopathy

Ramzi Amin, Muhammad Apriliandy Shariff, Petty Purwanita, Mgs Irsan Saleh — Sun, 10 Mar 2024 00:00:00 +0000

Purpose: To explore the effect of the flavonoid compounds of Andrographis paniculata by evaluating the glycemic profile, oxidative process, and inflammatory values in rats with diabetic retinopathy (DR).

Methods: An extract of A. paniculata was macerated with ethanol which yielded flavonoid compounds. Streptozotocin was utilized to induce diabetes mellitus in male Wistar rats. Vucetic’s methods were used to evaluate the retinal vessel diameters. Antioxidant parameters and inflammatory cytokines were assessed in retinal tissue.

Results: A funduscopic examination revealed some alterations in the retinal veins. In comparison to the DR group with no treatment, the diameter of the retinal vessels in the DR group that was treated with the flavonoid component of the A. paniculata extract (FAP) at doses of 20 and 40 mg/kg body weight (BW) was significantly smaller (P < 0.05), Glutathione, superoxide dismutase (SOD), and catalase levels were increased after receiving FAP at doses of 20 and 40 mg/kg BW (P < 0.05).

Conclusion: Administration of doses of 20 and 40 mg/kg BW of the A. paniculata’s flavonoid compounds improved DR in rats via retinal vessel diameter reduction, TNF-a and VEGF level reduction, and increasing antioxidants, SOD, catalase, and glutathione.

Polymeric Propranolol Nanoparticles for Intraocular Delivery: Formulation, Characterization, and Vitreous Pharmacokinetics

Sun, 10 Mar 2024 00:00:00 +0000

Purpose: Recent studies have reported the promising effect of intravitreal propranolol on retinal neovascularization. However, rapid clearance and short half-life of the drug in the vitreous are the main drawbacks of this therapeutic approach. This study investigates the extension of the residence time of propranolol in the vitreous by polymeric nanoparticles (NPs) with the prospect of improving choroidal neovascularization treatment.

Methods: The poly (lactic-co-glycolic) acid (PLGA) NPs were fabricated by a modified double emulsion solvent evaporation method and the obtained NPs were characterized for their size, poly dispersity index (PDI), and surface image. The in vitro release, cell cytotoxicity, and uptake of NPs were also evaluated. To investigate the effect of the vitreous pharmacokinetic drug loaded NPs versus that of the free propranolol, they were intravitreally injected into the rabbits’ eyes and the drug vitreous concentrations in defined intervals were analyzed by high performance liquid chromatography (HPLC).

Results: The spherical NPs with about 230 nm size, and almost 10% drug loading were obtained. Based on the 3-(4, 5-Dimethylthiazol-2-Yl)-2, 5-Diphenyltetrazolium Bromide (MTT) outcomes, 30 µg/ml of propranolol was considered as the guide dosage in the intravitreal injection. Confocal microscopy images verified the presence of labeled NPs in the posterior segment after five days of receiving the injection. In vivo assay revealed that the vanishing rate of propranolol in rabbits treated with propranolol NPs was reduced at twice the rate as compared to that of the vanishing rate experienced with only the free drug.

Conclusion: PLGA NPs can prolong the existence of propranolol in both vitreous and posterior ocular tissues, and thus, may provide an effective approach in treatment of posterior segment neovascularization.

Risk Factors for Retinopathy of Prematurity in Preterm Infants in Kerman, Iran

Sun, 10 Mar 2024 00:00:00 +0000

Purpose: Retinopathy of prematurity (ROP) is the main cause of blindness in premature infants. Despite developments in neonatal care and management guidelines, ROP is becoming increasingly prevalent worldwide. Hence, the identification of risk factors for ROP is critical to diminish the burden of the disease.

Methods: This cross-sectional study included all infants with gestational age ≤ 36 weeks referred to the ophthalmology clinic at Shafa hospital, Kerman, Iran from 2014 to 2015. Ophthalmologic examinations were performed followed by demographic and ophthalmic data collection and analysis.

Results: A total of 579 preterm neonates were screened including 325 boys and 254 girls. The incidence of ROP was 17.96%. Mean birth weight (BW) and gestational age (GA) were 1668.0 grams and 31.2 weeks, respectively. The results indicated that BW, GA, duration of hospitalization and oxygen therapy were significantly related to the development of ROP, however, after multivariate logistic regression analysis, only BW and duration of hospitalization remained significant. There were no significant associations between gender, type of delivery, or assisted reproductive technologies, and ROP (P = 0.461, 0.461, and 0.826, respectively).

Conclusion: BW and duration of hospitalization were significant risk factors for ROP in the current study. BW was also strongly associated with the need for therapy.

Modification of a Selective NTRK2 Agonist and Confirmation of Activity in a Glaucoma-on-a-Chip Model

Sun, 10 Mar 2024 00:00:00 +0000

Purpose: RNYK is a selective agonist of the neurotrophic tyrosine kinase receptor type 2 (NTRK2) which has been screened from a phage-displayed peptide library. Its sequence is SGVYKVAYDWQH, similar to a native NTRK2 ligand, that is, brain-derived neurotrophic factor (BDNF). The current study was performed to recognize and confirm critical residues for RNYK activity in a glaucoma-on-a-chip model.

Methods: We designed a modified RNYK (mRNYK) peptide based on hotspots of the RNYK sequence identified by alanine scanning. The critical residues consisted of tyrosine, valine, aspartic acid, and tryptophan (YVDW); however, lysine and glutamine were also maintained in the final sequence (YKVDWQ) for forming amide bonds and peptide dimerization. The affinity of mRNYK binding was confirmed by testing against NTRK2 receptors on the surface of ATRA-treated SH-SY5Y cells. The neuroprotective effect of mRNYK was also evaluated in cell culture after elevated pressure insult in a glaucoma-on-a-chip model.

Results: The primary amine on the lysine side-chain from one sequence (YKVDWQ) reacted with a γ[1]carboxamide group of glutamine from the other sequence, forming dimeric mRNYK. In silico, molecular dynamic simulations of the mRNYK–NTRK2 complex showed more stable and stronger interactions as compared to the RNYK–NTRK2 complex. In vitro, mRNYK demonstrated a neuroprotective effect on SH-SY5Y cells under normal and elevated pressure comparable to RNYK. The 50% effective concentration (logEC50) for mRNYK was 0.7009, which was better than RNYK with a logEC50 of 0.8318.

Conclusion: The modified peptide studied herein showed improved stability over the original peptide (RNYK) and demonstrated potential for use as a BDNF agonist with neuroprotective properties for treatment of neurodegenerative disorders such as glaucoma.

Sex Hormones Influence the Helmholtz–Kohlrausch Effect

Brian Foutch — Sun, 10 Mar 2024 00:00:00 +0000

Purpose: Saturated lights appear brighter than white lights of the same luminance. This is the Helmholtz–Kohlrausch (H–K) effect, and the phenomenon can be estimated by modeling achromatic luminance and saturation to total brightness. Current H–K effect models are different between women and men and are also more variable in women, which may be due to hormonal changes across the menstrual cycle (MC).

Methods: Total brightness (B) and achromatic luminance (L) were measured across blue, green, yellow-green, yellow, and red hues. These data were measured along with salivary hormone levels for nine cycling women and seven oral contraceptive (OC) users at points representing the menstrual, peri-ovulation, and luteal phases.

Results: Simple brightness/luminance (B/L) ratio estimates of the H–K effect did not differ by OC use or MC phase, but B/L ratios were higher for the red stimulus in cycling women than OC users during the luteal phase. Estrogen, progesterone, and their interaction predicted 18% of the variation in brightness for cycling women. For OC users, only estrogen could be fit to brightness models where it accounted for 5% of brightness variance.

Conclusion: These findings first provide clear support for separating cycling women from OC users, particularly when examining long-wavelength mechanisms. Next, the interaction of OC use and MC phase on B/L ratios for the red stimulus adds to a rich history of long-wavelength mechanisms. Lastly, the current result amends previous brightness models with multiple hormone terms for cycling women but not OC users.

The Effect of Cycloplegia on Ocular Alignment and AC/A Ratio

Sun, 10 Mar 2024 00:00:00 +0000

Purpose: The present study sets out to investigate the effect of cyclopentolate-induced cycloplegia on distance and near deviation and the accommodative convergence/accommodation (AC/A) ratio.

Methods: This prospective study was performed on 30 subjects. The inclusion criteria included a lack of any active ocular pathology and systemic diseases, no history of ocular surgery, and nonuse of various medications. Refraction, near and distance deviation were measured for all subjects, and the same examinations were repeated after the administration of two drops of cyclopentolate 1% to both eyes.

Results: The obtained data from 30 subjects, including 19 males, with a mean age of 22.53 ± 1.74 years were analyzed. The mean ± SD of near deviation in dry and cycloplegic conditions were – 6.9 ± 8.1 and +6.4 ± 9.1 prism diopters, respectively, which were statistically significant (P < 0.001). Distance deviation in cycloplegic conditions demonstrated an average difference of 0.8 prism diopters, compared to dry conditions (P < 0.001). AC/A ratios were 4.7 ± 2.5 and 9.7 ± 3.9 (Δ/D) in non-cycloplegic and cycloplegic conditions, respectively, which was a statistically significant difference (P < 0.001). The multiple regression indicated that among all under study variables, refraction (B coefficient: –2.4; P < 0.001) and near pre-cycloplegic deviation (B coefficient: 0.56; P < 0.001) were significantly associated with post-cycloplegic near deviation.

Conclusion: The results of this study indicated that cycloplegia causes a considerable esophoric shift in near deviation and a negligible esophoric shift in distance deviation. As a result, the AC/A ratio demonstrated a significant increase due to unequal changes in near and distance deviation.

Contemporary Approach to Narrow Angles

Wesam Shamseldin Shalaby, Rohit Reddy, Reza Razeghinejad, L. Jay Katz — Sun, 10 Mar 2024 00:00:00 +0000

Glaucoma is the leading cause of irreversible blindness worldwide. Among all glaucoma types,
primary angle closure glaucoma (PACG) affects approximately 23 million people worldwide, and
is responsible for 50% of glaucoma-related blindness, highlighting the devastating consequences
of this disease. The main mechanism of PACG is relative pupillary block. High-risk populations are
female gender, Asian ethnicity, high hyperopia, short axial length, and a thick/anteriorly positioned
lens. This review discusses the clinical diagnosis, classification, and management of patients with
a narrow angle with and without intraocular pressure (IOP) elevation and glaucomatous optic
nerve damage, including laser peripheral iridotomy (LPI), endocycloplasty (ECPL), lens extraction,
and goniosynechialysis.

A Framework for Future Analysis of Ophthalmology Fellowships in Iran: Call for Action, Implications and Recommendations

Mohammad Ali Javadi, Shima Tabatabai — Sun, 10 Mar 2024 00:00:00 +0000

Ophthalmology fellowship is focusing on the educational advancement, medical research progress and academic productivity by transforming general ophthalmologists into superior clinical capacities in ophthalmology. There is a vast majority of ophthalmologists who wish to undertake fellowship degrees. The fellowship programs have several benefits for ophthalmologists and medical institutions. However, the expansion of ophthalmic fellowships has resulted in a greater number of ophthalmology visits, the possibility of unnecessary subspecialty eye examinations, induced demand and increasing eye-care costs. Moreover, sub-specialized ophthalmic services are not accessible to patients in remote regions. This can lead to a degree of inequity in the provision of healthcare services in the healthcare system. The massive expansion of fellowships in ophthalmology is revitalizing the necessity for evaluation of the need for post[1]residency education and providing effective planning for the future of the ophthalmic human[1]resource for eye health. This narrative review includes an integration and descriptive summary of the existing evidence on trends and different aspects that affect the future of ophthalmic fellowship education. Moreover, we pinpointed challenges such as maintaining standards in fellowship education, keeping an efficient production of graduates, and improving productivity in both patient care and education. We explored potential solutions to overcome these challenges. The 7-step framework for future analysis suggested here includes Determining educational needs and desired outcomes, Evaluating the current status of fellowship education, determining the gaps, and appropriate solutions, analyzing possible future trends and their impact on ophthalmology practice, investing in virtual educational technology, developing new educational horizons by foresight expert panels, and human-resource planning.

A Novel Ornithine Aminotransferase Splice Site Mutation Causes Vitamin B6-Responsive Gyrate Atrophy

Sun, 10 Mar 2024 00:00:00 +0000

Purpose: Gyrate atrophy of the choroid and retina (GACR) is a rare congenital disorder and mutations in the ornithine aminotransferase (OAT) gene has been specified as the underlying cause. Patients show a high level of ornithine in body fluids which may be controlled by low protein diets. Pyridoxine (vitamin B6) supplementation may also be effective, however, most patients appear to be nonresponsive to this modality of treatment.

Case Report: Here, we report a characterized case of a vitamin B6-responsive GACR who had a splicing mutation in the OAT gene. The GACR diagnosis was confirmed through the clinical features, imaging, biochemical findings, and whole-exome sequencing (WES) results. WES data revealed the splicing mutation in intron 4 of the OAT gene (NM_001322967: c.425-1G>A).

Conclusion: Our knowledge about the diagnosis and treatment of GACR can be improved by identifying novel mutations in the OAT gene and accurate follow-up of the patients to determine how they respond to treatment.

Bilateral Optic Neuropathy Secondary to Intravenous Carboplatin Therapy

Arash Maleki, Mollie Lagrew, Elizabeth Slaney — Sun, 10 Mar 2024 00:00:00 +0000

Purpose: To report a case of carboplatin-induced bilateral optic neuropathy in a patient with metastatic squamous cell carcinoma of the tongue.

Case Report: A 65-year-old man with a history of squamous cell carcinoma of the tongue with metastasis to the right axillary lymph node treated with carboplatin and paclitaxel was evaluated for decreased visual acuity in both eyes. Visual acuity was 20/70 in the right eye and no light perception in the left eye. On dilated fundus examination, optic disc edema was present in both eyes with more severity in the left eye, flame shape hemorrhages around the optic nerve head in both eyes and cotton wool spots around the left optic nerve head. Brain and orbital MRI demonstrated enhancement of the bilateral optic nerve sheaths. He was diagnosed with bilateral carboplatin-induced optic neuropathy.

Conclusion: Our findings in this case justify monitoring of patients during their course of intravenous carboplatin therapy.

Low-cost Lateral Canthotomy and Cantholysis Model for the Emergency Department

David McMaster, Anas Khan — Sun, 10 Mar 2024 00:00:00 +0000

This is a Photo Essay and does not have an abstract. Please download the PDF or view the article in HTML.

Neuro-Ophthalmologic Complications of SARS-Cov-2 Infections and Vaccinations

Josef Finsterer, Fulvio Alexandre Scorza, Ana Claudia Fiorini — Sun, 10 Mar 2024 00:00:00 +0000

This is a Letter and does not have an abstract. Please download the PDF or view the article in HTML.