Medical hypothesis discovery and innovation in ophthalmology

Background: To analyze the academic characteristics, career trajectory, scholarly publications, and demographic background of the 100 most-cited authors in ophthalmic literature.
Methods: In this observational cross-sectional study, a database containing every ophthalmology journal article from 1967 to 2018 was built using Scopus journal article information. The 100 authors with the most citations were identified, along with a control group of authors with at least five publications. Information about each author, such as gender, institution, and educational degrees were found from online web searches. Intra- and inter-group analyses were performed to identify correlations that may lead to having a high level of impact in ophthalmology literature.
Results: Of the 100 most-cited ophthalmologists, 56 practice in the United States (US) and only 12 are female. In an odds ratio (OR) analysis, highly-cited researchers more often lived in the US (OR, 2.97; P < 0.001), were male (OR, 2.4; P = 0.02), and graduated from an elite medical school (OR, 3.89; P = 0.02) and/or residency (OR, 3.67; P = 0.02), but were not from an undergraduate institution (P = 0.75). There was no difference in citation numbers between different ophthalmology subspecialties (P = 0.22) or advanced degrees (PhD, MPH in addition to MD). Women among the top-100-cited authors were more likely to author high impact journal articles (P < 0.05).
Conclusions: Among highly-cited ophthalmologists, practicing in the US and attending a top medical school or residency program may provide training for a successful research career in ophthalmology. Additionally, top female ophthalmologists participate in more influential research.

Background: To determine if there is a difference in the quantity of microbial flora of the conjunctiva in individuals practicing head submersion (dunk) versus no head submersion (no-dunk) during hot tub use.
Methods: In this double-blind randomized clinical trial, healthy volunteers aged equally and more than 18 years were recruited. Participants were randomized to head submersion versus no head submersion during a 15-minute hot tub soak. Study personnel, masked to the dunk or no-dunk group assignment, obtained conjunctival cultures before and immediately after hot tub use. De-identified specimens were submitted to the clinical microbiology laboratory for culture and analysis. The main outcome measure was the difference in the quantity of organisms cultured from the conjunctiva before and after hot tub exposure, as determined using a defined ordinal scale. A two-tailed Student t-test was performed to compare the total microbial colony counts between the two arms. Simpson diversity was used to measure the changes in organism diversity between the arms.
Results: Of 36 enrolled subjects, 19 were randomly assigned to the dunk and 17 were assigned to the no-dunk groups. Water samples obtained from all hot tubs were culture negative. Eleven of 19 eyes (58%) from the dunk group and eight of 17 eyes (47%) from the no-dunk group had negative conjunctival bacterial cultures before and after hot tub exposure. However, six of 19 eyes (32%) and four of 17 eyes (24%) of the dunk and no-dunk groups, respectively, were culture-positive after, but not before hot tub exposure. The quantity of organisms before and after hot tub exposure was not significantly different between the two arms (P = 0.12). However, the dunk group only showed a small increase in the quantity of organisms after as compared to before hot tub use (P = 0.03). None of the samples from subjects or hot tubs were culture-positive for Acanthamoeba.
Conclusion: Head submersion in a public hot tubs during a 15-minute soak does not appear to change conjunctival flora, as determined by culture plate yield.

Background: Retinitis pigmentosa (RP), an inherited degenerative ocular disease, is considered the most common type of retinal dystrophy. Abnormalities of the photoreceptors, particularly the rods, and of the retinal pigment epithelium, characterizes this disease. The abnormalities progress from the midperiphery to the central retina. We here reviewed the developments in RP genetics in the last decade, along with its clinical features and natural course.
Methods: The present review focused on articles in English language published between January 2008 and February 2020, and deposited in PubMed and Google Scholar databases. We searched for articles reporting on the clinical manifestations and genes related to both syndromic and non-syndromic RP. We screened and analyzed 139 articles, published in the last decade, referring to RP pathogenesis and identified, summarized, and highlighted the most significant genes implicated in either syndromic or non-syndromic RP pathogenesis, causing different clinical manifestations.
Results: Recent literature revealed that approximately 80 genes are implicated in non-syndromic RP, and 30 genes in syndromic forms, such as Usher syndrome and Bardet Biedl syndrome (BBS). Moreover, it is estimated that 27 genes are implicated in autosomal dominant RP (adRP), 55 genes in autosomal recessive RP (arRP), and 6 genes in X-linked RP (xlRP), causing different RP phenotypes. Characteristically, RHO is the most prevalent adRP- and arRP-causing gene, and RPGR the most common xlRP-causing gene. Other important genes are PRPH2, RP1, CRX, RPE65, ABCA4, CRB1, and USH2A. However, different phenotypes can also be caused by mutations in the same gene.
Conclusions: The genetic heterogeneity of RP necessitates further study to map the exact mutations that cause more severe forms of RP, and to develop and use appropriate genetic or other effective therapies in future.

Background: This study aimed to evaluate the non-inferiority and safety of a newly developed preservative-free (PF) multi-dose latanoprost/timolol ophthalmic solution, compared with the benzalkonium chloride (BAK)-preserved fixed combination, in patients with open-angle glaucoma and ocular hypertension.
Methods: A Phase III randomized multi-center observer-blind parallel-group clinical trial was conducted. A total of 210 adult patients (aged over 18 years) were randomly treated with the PF- or the BAK-preserved latanoprost/timolol solution once daily in the affected eye(s) for 12 weeks. Follow-up visits were scheduled at weeks 2, 6, and 12; intraocular pressure (IOP) was recorded at 8:00 AM, 12:00 PM, and 4:00 PM. The primary efficacy endpoint to prove non-inferiority was the IOP change at 8:00 AM (± 1 hour) from the baseline to the end of treatment (week 12) in the studied eye. Safety parameters were also assessed.
Results: In total, 196 patients completed the study. The pressure-lowering effect of the PF eye drops was comparable to that of the preserved formulation at all time points. Latanoprost/timolol PF formulation was non-inferior to the BAK-preserved solution as shown by the change in IOP from day 0 to week 12. The point estimate of the inter-treatment difference was 0.624 mmHg (95% CI: -0.094, 1.341). Both treatments were well-tolerated during the study, and they had similar adverse event profiles.
Conclusions: PF-latanoprost/timolol combination was found to be non-inferior to the BAK-preserved formulation based on the efficacy at all times, with similar local tolerance.

Background: Retinoblastoma is the most common primary intraocular malignancy in children, although it is a rare neural retinal tumor. Improving the quality of life is the next goal after the primary medical goal of life preservation. The genotype-phenotype correlation may vary with the progression of retinoblastoma. Expressivity is determined by different RB1 gene mutations among individuals. Herein, we share our experience on the evaluation of the long-term progression of retinoblastoma, its treatment consequences, its impact on the quality of life, and how the underlying genotypes are related to the phenotypes. We provide a review of the relevant literature and present a case of a sporadic heritable bilateral retinoblastoma.
Case Presentation: We report the outcomes of a 28-year follow-up of a female diagnosed with an infantile disease. The patient's best eye, according to the tumor classification and genetic results, was treated conservatively whereas the worst eye was enucleated. On re-examinations, she had complications of the treatment she received. Therefore, another intervention was administered for several years. The patient's pathogenic variant and RB1 gene mutational inactivation were predispositions to the recurrence of the tumor and non-ocular primary malignancy. Nevertheless, the disease had no progression. The patient is stable despite her type of retinoblastoma, which is the sporadic heritable bilateral form.
Conclusions: Each phenotype of bilateral retinoblastoma varies in progression. The nature of the genetic mutation may determine its expressivity. It is of great significance to individualize every decision. In each case, the sequelae of the disease and treatment-induced complications may have an impact on the quality of the patient's life.

Background: The aim of this study was to test the non-inferiority of preservative-free (PF) latanoprost 50 micrograms per milliliter multi-dose ophthalmic solution versus the marketed benzalkonium chloride (BAK)-preserved latanoprost 50 micrograms per milliliter ophthalmic solution in patients with open-angle glaucoma and patients with ocular hypertension.
Methods: This was a prospective, national, randomized, multi-center, observer-blind, parallel-group controlled clinical trial. Patients were randomized to receive either PF or BAK-preserved latanoprost once daily for 12 weeks. The primary endpoint was the change in intraocular pressure (IOP) at 8:00 AM in the affected eye between the end of the treatment (week 12) and the baseline (week 0). Secondary measurements were taken at weeks 2 and 6, with IOP being recorded at 8:00 AM, 12:00 PM, and 4:00 PM.
Results: A total of 158 patients were included in the per protocol (PP) population (77 in the PF latanoprost treatment arm and 81 patients in the BAK-preserved latanoprost treatment arm). PF latanoprost was non-inferior to BAK-preserved latanoprost in reducing IOP at 8:00 AM in the study eye from the baseline (week 0) to the end of the treatment (week 12). The point estimate of the between-treatment difference was 0.1 mmHg (95% confidence interval: -0.646, 0.847). Mean between-group differences in IOP reduction from the baseline to each of the secondary measurements were also similar between the two treatment arms. The two treatments were well tolerated and had comparable adverse event profiles.
Conclusions: PF latanoprost was non-inferior to BAK-preserved latanoprost in reducing IOP in patients with open-angle glaucoma or ocular hypertension. Both treatments were well tolerated.