Aims and Scope
Founded in the summer of 2020, Medical hypothesis, discovery & innovation in optometry, is an international, open-access, double-blinded peer-reviewed, quarterly journal that considers publications related to optometry. The aim is to present a scientific medium of communication for researchers in the field of optometry. The journal is of interest to a broad audience of visual scientists and publishes original articles, reviews, case reports, and commentaries after a rigorous peer-review process with more interest in original articles. The journal is affiliated with and published by the "IVORC" (Registration File Number: 803630055), a registered non-profit corporation in Austin, Texas, United States. We provide English editing for papers as a complimentary free-of-charge service.

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Rhegmatogenous retinal detachment: an analysis of 2315 eyes over a six-year period

Farzan Kianersi, Yousef Barati, Hamidreza Kianersi, Heshmatollah Ghanbari, Hasan Razmjoo, Farhad Fazel, Alireza Dehghani, Mohammadreza Akhlaghi, Ali Salehi, Hanieh Kianersi, Mohsen Pourazizi

Medical hypothesis, discovery & innovation in optometry, Vol. 4 No. 4 (2023), 25 December 2023 , Page 148-156

Background: Rhegmatogenous retinal detachment (RRD) is a form of retinal detachment caused by passage of fluid from the vitreous cavity into the space between the neurosensory retina and the retinal pigment epithelium via a retinal break or full-thickness defect. At our tertiary referral center, we evaluated the clinical and epidemiological features of RRD, and we herein report the frequency of related risk factors.
Methods: In this retrospective study, we reviewed the records of patients with a final diagnosis of RRD at an academic ophthalmological referral center in Isfahan, Iran, over a six-year period. We retrieved and reviewed data from the medical records of all eligible participants, including sex, age, laterality, lens status, macular status, type of RRD, location and number of breaks, type of surgery, rate of re-operation during the first year after initial surgery, and documented clinical risk factors for RRD. Clinical risk factors were categorized as the presence of myopic refractive error, ocular trauma, history of cataract surgery, history of other ocular surgeries, history of uveitis, or undetermined.
Results: We included 2315 eyes of 2229 patients with a mean (standard deviation [SD]) age of 51.1 (16.9) years and a male-to-female ratio of 1.8:1. The most common quadrants containing retinal breaks were the superotemporal quadrant (34.1%), inferotemporal quadrant (23.4%), and superonasal quadrant (10.7%). Macula-involved RRD was seen in 90% of eyes (n=2083 eyes). The most frequently identified risk factors were cataract surgery (32.9%) and myopia (22.3%) in adults, and myopia (35.0%) and ocular trauma (27.4%) in the pediatric group. Most eyes underwent pars plana vitrectomy (51.3%), whereas pneumatic retinopexy (0.7%) was the least commonly selected.
Conclusions: Our results indicate that cataract surgery and myopia are the most common risk factors for RRD in adults. Myopia and ocular trauma are the most common risk factors in pediatric patients. As observed in many studies, the characteristics of the study population, including middle age, male sex, myopia, and ocular trauma, may be associated with RRD at different rates. Further population-based longitudinal studies with larger sample sizes are required to verify these preliminary observations.

Contralateral eye comparison of the efficacy and safety of two artificial tear formulations for corneal subbasal nerve fiber regeneration after photorefractive keratectomy

Noor Shazana Md Rejab, Mohd Radzi Hilmi, Khairidzan Mohd Kamal, James S Wolffsohn

Medical hypothesis, discovery & innovation in optometry, Vol. 4 No. 4 (2023), 25 December 2023 , Page 157-165

Background: Currently, artificial tears (ATs) are the first-line agents for managing dry eye disease (DED). This study compared the efficacy and safety of two different AT formulations, Systane® Hydration (SH) and Systane® Ultra (SU), on symptoms of DED and regeneration of the subbasal corneal nerve fiber length (CNFL) in photorefractive keratectomy (PRK)-treated eyes.
Methods: This prospective contralateral comparative study recruited myopic eyes scheduled for PRK, and either SH or SU were administered for up to 3 months postoperatively. All participants underwent a standard comprehensive preoperative ophthalmological examination, in vivo confocal microscopy to evaluate the subbasal CNFL, and completed Ocular Surface Disease Index (OSDI) questionnaire for assessing dry eye symptoms. Image analysis software was used to calculate the subbasal CNFL (micrometer/mm2). Assessments were repeated at the 1- and 3-month follow-up visits. Pre- and postoperative subbasal CNFL and OSDI scores were compared to determine inter- and intra-group differences.
Results: Fifty eyes of 25 participants were included in this study. The mean (standard deviation) age of the participants was 22.7 (3.8) years. The OSDI scores for both groups increased significantly at 1 month (both P<0.05), followed by a decrease at 3 months to values comparable to the preoperative scores (both P>0.05). Although OSDI scores were comparable at baseline and at the 1-month postoperative visit (both P>0.05), the SU-treated eyes had a significantly better OSDI score at the 3-month visit (P<0.05), despite being clinically insignificant. Preoperative subbasal CNFL differed significantly between the groups (P=0.001), yet the mean values at both postoperative visits were comparable (both P>0.05). In both groups, subbasal CNFL was significantly reduced at 1 month, followed by a significant increase at the 3-month postoperative visit compared to baseline (all P<0.05). No treatment-related complications were observed at the end of the study period.
Conclusions: No significant difference was found between the preoperative and 3-month postoperative OSDI scores in the SH- or SU-treated eyes. Subbasal CNFL regeneration indicated a positive effect of both ATs, with a longer mean CNFL noted in the SH-treated eyes at the final visit. This suggests that SH may be a better option for improving corneal reinnervation after PRK. These observations must be verified in further trials with longer follow-up periods and larger sample sizes.

Effects of repeated intravitreal bevacizumab administration on anterior segment parameters and limbal stem cells

Mojtaba Eidizadeh, Mohsen Felegary, Seyed Hamid Madani, Fatemeh Hosseini, Masood Bagheri

Medical hypothesis, discovery & innovation in optometry, Vol. 4 No. 4 (2023), 25 December 2023 , Page 166-173

Background: Macular edema (ME) is fluid accumulation in the macula caused by vascular leakage. Repeated intravitreal bevacizumab (IVB) injections are extensively used to treat ME of different origins, are well tolerated, and have few side effects. This study evaluated the effects of repeated IVB injections on the anterior segment parameters and limbal stem cells (LSCs) in eyes with ME.
Methods: This before–after study involved patients with ME of different causes who underwent repeated IVB injections at the Imam Khomeini Ophthalmology Center in Kermanshah, Iran. Before and after repeated IVB injections, anterior segment parameters were measured using anterior segment optical coherence tomography, and the LSCs were assessed using impression cytology.
Results: We enrolled 42 eyes of 42 patients with a mean (standard deviation [SD]) age of 59.6 (7.6) years, of whom 25 (59.5%) were men and 17 (40.5%) were women. The underlying diseases included diabetic ME in 30 eyes (71.4%), central (5 [11.9%]) or branch (3 [7.1%]) retinal vein occlusion, and choroidal neovascularization in 4 eyes (9.5%). The right eye was affected in 22 (52.4%) participants. The mean (SD) number of IVB injections was 4.3 (1.3). After repeated injections, the mean central corneal thickness (CCT) increased, whereas the mean anterior chamber angle (ACA) and anterior chamber depth (ACD) decreased (all P<0.001). Three patients developed LSC deficiency after repeated IVB injections for diabetic ME.
Conclusions: We observed a significant increase in the mean CCT and a decrease in the mean ACA and ACD after repeated IVB injections in our series. Three patients developed LSC deficiency after repeated IVB injections for diabetic ME management. The observed effect on LSC may cast doubt on the safety of repeated IVB injections; however, this finding must be verified in multicenter clinical trials with longer follow-up periods and larger study samples.

Association of WDR36 polymorphisms with primary open-angle glaucoma

Pragati Garg, Mehvish Malik, Tasleem Raza

Medical hypothesis, discovery & innovation in optometry, Vol. 4 No. 4 (2023), 25 December 2023 , Page 174-180

Background: Various genes contribute to the pathophysiology of primary open-angle glaucoma (POAG). The WD repeat domain 36 (WDR36) gene may participate in T cell activation and, hence, in the pathogenesis of POAG. We investigated the association of two WDR36 gene single nucleotide polymorphisms (SNPs) with POAG.
Methods: This cross-sectional study recruited patients aged >40 years with POAG and investigated the rs10038177 and rs1971050 SNPs of WDR36 using polymerase chain reaction and direct DNA sequencing. All participants underwent comprehensive ocular examination, visual field assessment using the Swedish Interactive Threshold Algorithm standard 24-2 threshold test, and measurement of peripapillary retinal nerve fiber layer thickness (RNFLT) using spectral domain optical coherence tomography.
Results: We enrolled 105 patients with a mean (standard deviation) age of 55.41 (8.56) years and a male-to-female ratio of 56 (53.3%) to 49 (46.7%), most of whom had a diagnosis of POAG for 2 to 5 years (60.0%). Most participants had diabetes (90.5%) but not hypertension (88.6%). There was a significant association of rs10038177 (P<0.05), but not rs1971050 (P>0.05), with family history of glaucoma. The association between rs10038177 and intraocular pressure was significant (P<0.05), but that between rs1971050 and intraocular pressure was not (P>0.05). No significant association was observed between mean cup-to-disc ratio and either SNP (both P>0.05). For rs10038177, a significant association was found only with the RNFLT of the superior quadrant (P<0.05), whereas for rs1971050, a significant association was found with the RNFLT of all four quadrants and average RNFLT (all P<0.05). However, pairwise comparisons revealed no significant differences between genotypes (P>0.05 for all pairwise comparisons). The association of rs10038177 with glaucoma severity was insignificant (P>0.05), and most patients with the TC genotype (71.7%) had moderate severity. There was no significant association between rs1971050 and glaucoma severity (P>0.05).
Conclusions: We observed genetic links between some, but not all, characteristics of POAG and the rs10038177 and rs1971050 SNPs of WDR36. Follow-up studies on these and other WDR36 SNPs in populations with different genetic backgrounds are necessary to confirm this genetic association.

Photophysical and photodynamic analysis of different formulations of riboflavin

Matias Osaba, Tomas Cristian Tempesti, Victor Eduardo Reviglio

Medical hypothesis, discovery & innovation in optometry, Vol. 4 No. 4 (2023), 25 December 2023 , Page 181-187

Background: Riboflavin (Rb) has been used in the ophthalmological procedure known as corneal cross-linking (CXL). Pathologies requiring this treatment include keratoconus, corneal ectasia, and infectious keratitis. Rb is instilled via different molecules that are transported into the tissues. However, each vehicle imparts different properties that alter the photodynamic behavior of Rb, leading to variable concentrations of free radicals within the medium. The objective of this study was to measure the concentrations of free radicals produced by commonly used Rb formulations. To determine the free radical production level of each formulation, L-tryptophan (L-Tryp) was used as a model substrate because it can be efficiently photo-oxidized.
Methods: We investigated the photodegradation of L-Tryp and its kinetics upon light exposure. The spectra were recorded using a Shimadzu UV-1800 PC spectrophotometer and a Cary Eclipse fluorescence spectrophotometer. A high-power solid-state LED light source was used for irradiation. L-Tryp degradation was performed using a 9-W LED lamp, and steady-state photolysis was conducted in quartz cells. The observed rate constants for L-Tryp degradation were determined by analyzing the changes in absorbance and fluorescence intensity. Data analysis was performed using Origin software.
Results: We examined the characteristics of the photophysical and photodynamic action of the carriers in different commercially available Rb formulations. These included a) Rb with dextran, b) Rb without dextran, c) VibeX Rapid® (hydroxypropylmethylcellulose as a vehicle), d) Trans-Epithelial Kit (I) (sodium chloride as a vehicle), and e) Trans-Epithelial Kit (II) (benzalkonium chloride as a vehicle), using L-Tryp as a model substrate, and focusing on absorption and emission spectra. VibeX Rapid® exhibited the highest photo-degradation constant. The study affirmed the stability of Rb formulations for CXL and highlighted the efficacy of VibeX Rapid® in L-Tryp photo-oxidation and this rationalizes its current use as a CXL agent.
Conclusions: We demonstrated that formulations for transport of Rb are of crucial importance in CXL applications. Rb in the VibeX Rapid® formulation is more effective in generating photo-degradation, and this reflects its superior performance in CXL. Future experiments should be designed and conducted to quantitatively differentiate the production of free radicals. Studies involving human participants could shed light on the clinical efficacy and safety of the available Rb formulations.

Hypothetical proposal for the course of retinal blood vessels in the posterior pole—description and its clinical implications

Pradeep Venkatesh

Medical hypothesis, discovery & innovation in optometry, Vol. 4 No. 4 (2023), 25 December 2023 , Page 188-194

Background: Branch retinal vein occlusion (BRVO) is the second-most common retinal vascular disorder. Arteriosclerotic changes at the site of obstruction and hemodynamic turbulence within the vessels are considered risk factors. Overcrossing of the vein by an artery has traditionally been considered to increase the risk of BRVO. Recent studies using optical coherence tomography and optical coherence tomography angiography have suggested a higher prevalence of vein-over-artery crossings in this disease. Nevertheless, uncertainty persists as to why some patients, even those with the same disease duration, have varying degrees of venous dilation and develop sufficient collaterals, while others develop substantial ischemia and its sequelae.
Hypothesis: Herein, it is hypothesized that because retinal blood vessels are transparent, tubular, and collapsible conduits coursing over a hollow spherical surface, the changes related to AV crossings over the entire course of a vessel, rather than at any single isolated crossing, could contribute to the risk, natural progression, and outcomes of BRVO. The study analyzed color fundus photographs from two image datasets. The first dataset comprised 100 randomly selected images from the author’s own collection at the Rajendra Prasad Center for Ophthalmic Sciences. The second dataset comprised 100 images from the MESSIDOR database; three images were excluded owing to poor focus. Using 394 observations from 197 retinal photographs, four distinct patterns of AV crossing along the course of blood vessels were recognized: (A and B) wicker basket, (C) straight, (D) widely spaced, and (E) indeterminate. The percentages of tight wicker, loose wicker, straight, widely spaced, and indeterminate patterns in the two image sets were 19% (38/200) and 16.5% (32/194), 22.5% (45/200) and 27.8% (54/194), 16.5% (33/200) and 15.5% (30/194), 22.5% (45/200) and 28.4% (55/194), and 19.5% (39/200) and 11.9% (23/194), respectively. Hence, the wicker basket pattern was the most common AV crossing pattern in both image sets.
Conclusions: The wicker basket pattern may provide structural stability and aid in maintaining pressure gradients within the retinal vascular bed. This observation of variable AV relationships at consecutive crossings may improve our understanding of the pathogenesis, natural history, and outcomes of BRVO. Future longitudinal studies including patients at risk of BRVO, or retrospective analyses of patients with BRVO who had ophthalmic examinations and archived fundus images before the vascular event, should verify the relevance of these observed vascular patterns.