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O TM-J, Ceisler E, Broude C, Chan K, Pacicco L, Fay A, Waner M. Distribution and Clinical Characteristics of Periorbital Infantile Hemangiomas. Facial Plast Surg Aesthet Med 2023;25(2):172-178.Abstract
Background: Periorbital infantile hemangiomas (POIHs) are associated with a high incidence of visual complications. Objective(s): To analyze the sites of predilection of POIHs and to determine whether certain sites require earlier intervention due to their higher rate of visual complications. Methods: A retrospective case series study was conducted on patients from two tertiary care centers for 25 years. The location of POIHs was determined from clinical photographs, medical records, and radiological studies. The presence or absence of anisometropic astigmatism (anisoastigmatism) and amblyopia was recorded. Data were analyzed using a chi-square test. Results: There were 486 patients, of which 302 patients had ophthalmology evaluations and 245 patients had refractive error data. At presentation, 10% of patients already had amblyopia and 44% had anisoastigmatism. Medial eyelid lesions had the highest risk of developing anisoastigmatism (anisoastigmatism correlates with eyelid position, p = 0.0001). Segmental and upper medial lesions had the highest risk of amblyopia at initial evaluation. Conclusion: The site of POIH is an important indicator for developing clinically significant anisoastigmatism and amblyopia, underlining the need for early ophthalmologic assessment and management.
Chorfi S, Place EM, Huckfeldt RM. Disparities in Inherited Retinal Degenerations. Semin Ophthalmol 2023;38(2):201-206.Abstract
To review disparities in the field of inherited retinal degenerations to establish foundations for future discussions oriented toward finding possible solutions. A narrative overview of the literature. Despite collective efforts towards democratization of genetic testing and investigation, genetic databases containing primarily European populations are heavily relied upon. Access to specialized care and other resources is also still not available to all. Recognizing and addressing disparities and inequities within the field of inherited retinal degenerations will improve our care of these patients and our knowledge of their conditions.
Vaccaro S, Bosio L, Parekh M, Gadhvi KA, Giannaccare G, Scorcia V, Semeraro F, Kaye SB, Romano V. Surgical goniolens for tag identification and removal in DMEK surgery. Eur J Ophthalmol 2023;33(3):1480-1483.Abstract
INTRODUCTION: We describe a novel technique for identifying endothelial Descemet membrane (DM) tags remaining after descemetorhexis in patients undergoing Descemet membrane endothelial keratoplasty (DMEK) surgery. METHODS: A surgical goniolens is applied to the corneal surface after descemetorhexis in order to visualize the peripheral inner corneal layer at 360° and identify endothelial-DM tags. RESULTS: A detailed visualization of the peripheral inner corneal layer is possible using goniolens, without using any staining in the anterior chamber. CONCLUSION: The technique may be used to screen the posterior corneal surface for any retained endothelial-DM tags. It may to lower the risk of remaining tags and indirectly lower the incidence of DMEK graft detachment.
Singh RB, Li J, Parmar UPS, Jeng BH, Jhanji V. Vaccine-associated corneal graft rejection following SARS-CoV-2 vaccination: a CDC-VAERS database analysis. Br J Ophthalmol 2023;108(1):17-22.Abstract
PURPOSE: To evaluate the cases of corneal graft rejection following SARS-CoV-2 vaccination reported to Centers for Disease Control and Prevention Vaccine Adverse Event Reporting System. METHODS: A descriptive analysis of the demographics, clinical history and presentation was performed. We evaluated the correlation between the vaccines and duration of vaccine-associated graft rejection (VAR) onset following vaccination using a one-way analysis of variance test. A post hoc analysis was performed between VAR onset-interval following vaccination dose and vaccine type. Finally, a 30-day cumulative incidence analysis was performed to assess the risk of VAR in short term following different doses, vaccines and type of corneal transplantation. RESULTS: A total of 55 eyes of 46 patients were diagnosed with VAR following vaccination with BNT162b2 (73.91%) and mRNA-1273 (26.09%). The mean age of the patients was 62.76±15.83 years, and 28 (60.87%) were female. The patients diagnosed with VAR had undergone penetrating keratoplasty (61.82%), Descemet membrane endothelial keratoplasty (12.73%), descemet stripping endothelial keratoplasty (18.18%), anterior lamellar keratoplasty (3.64%) and corneal limbal allograft transplantation (1.82%). The mean time for VAR since penetrating and endothelial keratoplasty was 8.42±9.23 years and 4.18±4.40 years, respectively. 45.65% of the cases of VAR were reported after the second dose of vaccine. The duration of VAR onset was significantly shorter after the second dose compared with the first and booster doses (p=0.0165) and in patients who underwent endothelial keratoplasty compared with penetrating keratoplasty (p=0.041). CONCLUSIONS: This study outlines a possible temporal relationship between corneal graft rejection and SARS-CoV-2 vaccination. An earlier onset of VAR was observed in patients who had a history of endothelial keratoplasty and following the second dose of vaccination.
Gluckstein J. Diversity in Academic Ophthalmology: Disparities and Opportunities from Medical School to Practice. Semin Ophthalmol 2023;38(4):338-343.Abstract
INTRODUCTION: Compared to the United States population as a whole, physicians are more likely to identify as men, identify as Asian or non-hispanic White, and be raised in wealthier households. Racial, ethnic, gender, and socioeconomic representation in ophthalmology is often blamed on the pipeline of matriculants. METHODS: This review collects recent data from the US census, AAMC, and primary literature on gender, racial, ethnic, and socioeconomic diversity from medical school to ophthalmology practice. RESULTS: Data from the medical and ophthalmology literature shows that medical students are less diverse than medical school applicants, ophthalmology residencies are less diverse than graduating medical students, and ophthalmology departments are less diverse than those of most other specialties. DISCUSSION: At each level, there are limitations in representation beyond the pipeline of medical school applicants or medical students applying to ophthalmology. There are many practical steps the field can take at each level of training to move the specialty toward more equitable representation.
Baker CW, Josic K, Maguire MG, Jampol LM, Martin DF, Rofagha S, Sun JK, Sun JK. Comparison of Snellen Visual Acuity Measurements in Retinal Clinical Practice to Electronic ETDRS Protocol Visual Acuity Assessment. Ophthalmology 2023;130(5):533-541.Abstract
PURPOSE: Evaluate the differences between clinical visual acuity (VA) as recorded in medical records and electronic Early Treatment Diabetic Retinopathy Study (eETDRS) protocol VA measurements and factors affecting the size of the differences. DESIGN: Retrospective chart review. PARTICIPANTS: Study and fellow eyes of participants enrolled in DRCR Retina Network Protocols AC and AE (diabetic macular edema), and W (nonproliferative diabetic retinopathy) with clinical VA recorded within 3 months before the protocol visit. METHODS: Differences and their association with patient and ocular factors were evaluated using linear mixed models with random effects for correlations within sites and participants. MAIN OUTCOME MEASURE: Difference between VA letter scores measured by eETDRS during a study visit versus measured by Snellen during a regular clinical visit (Snellen fraction converted to eETDRS). RESULTS: Data from 1016 eyes (511 participants) across 74 sites were analyzed. The mean VA measurements were 68.6 letters (Snellen equivalent 20/50) at the clinical visit and 76.3 letters (Snellen equivalent 20/32) at the protocol visit, with a mean (standard deviation [SD]) of 26 (21) days between visits. Mean (SD) protocol VA was better than clinical VA by 7.6 (9.6) letters overall, 10.7 (12.6) letters in eyes with clinical VA ≤ 20/50 (n = 376), and 5.8 (6.6) letters in eyes with clinical VA ≥ 20/40 (n = 640). On average, the difference between clinical and protocol VA was 1.3 letters smaller for every 1-line (5 letters) increase in clinical VA (P < 0.001). Mean (SD) differences by clinical correction of refractive error were 3.9 (9.0) letters with refraction, 6.9 (9.2) letters with glasses/contact lenses, 7.9 (11.5) letters with pinhole, and 9.8 (9.3) letters without correction (P = 0.06). CONCLUSIONS: On average, clinical Snellen VA is 1 to 2 lines worse than eETDRS protocol refraction and VA testing, which may partly explain why clinical practice does not always replicate clinical trial results. Eyes with lower clinical measurements and eyes tested without clinical refraction tended to have larger differences. Considering the potential discrepancies between clinical and protocol VA measurements, refracting eyes in the clinic may benefit patients when determining treatment plans and study referrals based on vision. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
Hennein L, Jastrzembski B, Shah AS. Use of Telemedicine in Pediatric Ophthalmology in the Underserved Population. Semin Ophthalmol 2023;38(2):116-123.Abstract
Access to pediatric eye care is critical in diagnosing and treating eye disease promptly to prevent visual impairment. The demand for pediatric ophthalmology is high, even in developed countries, and significant socioeconomic disparities exist in access to care. The purpose of this article is to summarize the current literature on the use of telemedicine in pediatric ophthalmology in the underserved population and to identify areas of opportunity. A detailed literature review was performed in PubMed and Google Scholar on October 1, 2021. All articles in English that described the use of telemedicine in pediatric ophthalmology, with particular attention to the underserved pediatric population, were included. There is a paucity of literature on the visual outcomes from pediatric teleophthalmology alone, and even less in underserved populations specifically. Literature supports its use in subacute to chronic eye disease, return and postoperative visits, and screening for retinopathy in prematurity in particular. Collaboration between pediatric optometrists and pediatric ophthalmologists for both asynchronous and synchronous care delivery models has shown promise in several studies. It is essential to operate within the limits of pediatric teleophthalmology and utilize this valuable service for its strengths. Telemedicine may expand access to pediatric ophthalmologists in underserved populations and may reduce the burden of eye disease.
Viola P, Neri E, Testa V, Parekh M, Cian R, Grassetto A, Romano V. Clinical Outcomes of Preloaded Descemet Membrane Endothelial Keratoplasty With Endothelium Inward: A 24-Month Comparative Analysis Between Fuchs Endothelial Corneal Dystrophy and Bullous Keratopathy. Cornea 2023;42(9):1133-1139.Abstract
PURPOSE: The aim of this study was to compare long-term clinical outcomes of preloaded Descemet membrane endothelial keratoplasty (DMEK) between Fuchs endothelial corneal dystrophy (FECD) and bullous keratopathy (BK). METHODS: In this single-center retrospective clinical case series, 71 eyes of 64 patients indicated with FECD (62%) or BK (38%) (with or without cataract) were treated with preloaded DMEK grafts between March 2018 and February 2020. Standard DMEK peeling, followed by manual folding of the tissue with endothelium-inward orientation and storing in a preloaded fashion inside a 2.2-mm intraocular lens cartridge. All tissues were delivered using a bimanual pull-through technique, followed by air tamponade. Graft unfolding time, endothelial cell loss, corrected distance visual acuity, central corneal thickness, rebubbling rate, and intraoperative and postoperative complications at 1, 3, 6, 12, and 24 months were recorded. RESULTS: The mean intraoperative graft unfolding time in FECD did not differ from the BK group ( P = 0.6061). Cystoid macular edema did not differ in either group ( P = 0.6866). The rebubbling rate was found to be significantly higher in FECD compared with the BK group ( P = 0.0423). Corrected distance visual acuity significantly improved at the first month after surgery ( P = 0.0012), with no differences between FECD and BK at 24 months ( P = 0.2578). Central corneal thickness was stable postoperatively and showed no differences between the groups ( P = 0.3693). Significantly higher endothelial cell counts were observed in the FECD group at 24 months ( P = 0.0002). CONCLUSIONS: Preloaded DMEK with "endothelium-in" offers acceptable intraoperative time, rebubbling rate, and clinical outcomes in both FECD and BK groups. Patients with FECD show better postoperative clinical outcomes even if the rebubbling rate is relatively high.
Makhoul KG, Bitar RA, Armstrong GW, Weinert MC, Ivanov A, Kahale F, Ta T, Lorch AC. Effect of time to operative repair within twenty-four hours on visual acuity outcomes for open globe injuries. Eye (Lond) 2023;37(11):2351-2355.Abstract
PURPOSE: Convention is to perform open globe injury (OGI) repair within 24 h to minimize risk of endophthalmitis. However, there are limited data assessing how time to operative repair (OR) within 24 h impacts postoperative visual acuity (VA). METHODS: Manual retrospective chart review of 633 eyes at Massachusetts Eye and Ear (MEE) with a diagnosis of OGI between 2012 and 2022. Inclusion criteria were primary repair ≤ 24 h after injury and ≥1 month follow-up. Multivariate regression analysis was conducted with postoperative VA as primary outcome. RESULTS: Of the subjects, 489 (77.3%) were male and 496 (78.4%) were white. Demographics of OGI wounds included 320 (50.6%) rupture and 313 (49.4%) laceration; 126 (19.9%) with rAPD, 189 (29.9%) zone 3 injuries, 449 (71.2%) uveal prolapse, and 110 (17.4%) intraocular foreign body. Final postoperative LogMAR VAs consisted of 31% with a VA < 1.7, 9% with a VA of 1.9, 18% with a VA of 2.3, 27% with a VA of 2.7, and 11% with a VA of 3.0. Multivariate analysis showed no significant correlation between time to OR and postoperative VA (p = 0.800) [95%CI: -0.01,0.01]. Older age (p < 0.001) [95%CI: 0.00,0.01], worse presenting VA (p < 0.001) [95%CI: 0.17,0.32], rAPD (p < 0.001) [95%CI: 0.65,1.0], mechanism of rupture (p < 0.001) [95%CI: 0.19,0.54], higher zone of injury (p < 0.001) [95%CI: 0.25,0.45], and uveal prolapse (p = 0.003) [95%CI: 0.09,0.42] were significantly associated with worse final VA. CONCLUSIONS: Time to repair of OGIs within 24 h does not influence final VA. Optimization of surgical and patient factors may contribute more significantly to final VA than prioritizing more rapid time to OR.
Qureshi S, Dohlman TH. Penetrating Keratoplasty: Indications and Graft Survival by Geographic Region. Semin Ophthalmol 2023;38(1):31-43.Abstract
Corneal transplantation, or penetrating keratoplasty (PK), is the most common form of solid-organ transplantation performed worldwide. Here, we evaluated the indications for PK and rates of transplant survival around the world by geographic region. We conducted a literature search of PubMed, MEDLINE, and Google Scholar databases and identified 155 relevant studies from 41 countries published between 1987 and 2021. The most common indications for PK were keratoconus in Europe, Africa, the Middle East, Australia, New Zealand, and Central and South America, bullous keratopathy in North America, and corneal scarring in Asia. The overall global mean graft survival rates at 1-, 2-, 3-, 5-, and 10-years were 88.6%, 81.2%, 78.9%, 72.8%, and 61.2%, respectively. Through this systematic analysis of PK by region, we hope to bring a new perspective to the corneal transplantation literature and to potentially highlight global differences and unmet needs in patient care.
Liu C, Saeed HN. Disparities in Access to Corneal Tissue in the Developing World. Semin Ophthalmol 2023;38(2):183-189.Abstract
Corneal disease is a leading cause of blindness worldwide. For most blinding corneal conditions, keratoplasty is the only way of restoring sight. Unfortunately, access to corneal transplantation is widely variable, most notably due to the lack of suitable donor material. There exists significant disparity between the developed and developing world when it comes to access to cornea tissue, with supply often inversely proportional to burden of disease. The purpose of this review is to identify the current disparities in supply and demand of corneal donor tissue, understand how to access corneal tissue, and propose solutions that promote equitable care for patients with severe corneal disease.
Hu B, Huang Y, Jakobs TC, Kang Q, Lv Z, Liu W, Wang R. Viability of mitochondria-labeled retinal ganglion cells in organotypic retinal explant cultures by two methods. Exp Eye Res 2023;226:109311.Abstract
Retinal explant cultures provide a valuable system to study retinal function in vitro. This study established a new retinal explant culture method to prolong the survival of retinal ganglion cells (RGCs). Explants were prepared in two different ways: with or without optic nerve. Retinas from newborn mice that had received an injection of MitoTracker Red into the contralateral superior colliculus to label axonal mitochondria were cultured as organotypic culture for 7 days in vitro. At several time points during the culture, viability of RGCs was assessed by multi-electrode array recording, and morphology by immunohistochemical methods. During the culture, the thickness of the retinal tissue in both groups gradually decreased, however, the structure of the layers of the retina could be identified. Massive apoptosis in the retinal ganglion cell layer (GCL) appeared on the first day of culture, thereafter the number of apoptotic cells decreased. Glial activation was observed throughout the culture, and there was no difference in morphology between the two groups. RGCs loss was exacerbated on 3rdday of culture, and RGCs loss in retinal explants with preserved optic nerve was significantly lower than in retinas that did not preserve the optic nerve. More and longer-lasting mitochondrial signals were observed in the injured area of the optic nerve-preserving explants. Retinal explants provide an invaluable tool for studying retinal function and developing treatments for ocular diseases. The optic nerve-preserving culture helps preserve the integrity of RGCs. The higher number of mitochondria in the nerve-preserving cultures may help maintain viability of RGCs.
Rudnick ND, Vingopoulos F, Wang JC, Garg I, Cui Y, Zhu Y, Le R, Katz R, Lu Y, Patel NA, Miller JB. Characterising collateral vessels in eyes with branch retinal vein occlusions using widefield swept-source optical coherence tomography angiography. Br J Ophthalmol 2023;107(12):1887-1891.Abstract
BACKGROUND/AIMS: To characterise the morphology, location and functional significance of both macular and extramacular collateral vessels (CVs) in patients with a history of branch retinal vein occlusion (BRVO) using widefield swept-source optical coherence tomography angiography (WF SS OCTA). METHODS: Patients with a history of BRVO underwent WF SS OCTA testing to acquire 12×12 mm images, which were evaluated for CVs and non-perfusion area (NPA). Region of interest analysis of individual CVs was performed to identify correlations between CV size, depth and retinal location. Mixed effects multivariate regression analyses of factors associated with NPA and visual acuity (VA) were performed. RESULTS: Fifty-five CVs were identified in 28 BRVO eyes from 27 patients. CVs were identified in 42.9% (12/28) of eyes with a history of BRVO, and of these, 45.5% (25/55) were extramacular. The majority of CVs (87.3%, 48/55) coursed through both the superficial and the deep capillary plexus (DCP), while a subset (12.7%, 7/55) were strictly superficial. No CVs were found to course strictly through the DCP alone. CV depth increased with distance from the optic disc (p=0.011) and CV size increased with distance from the fovea (p=0.005). There were no statistically significant associations between CVs and NPA, or between CVs and VA. CONCLUSIONS: WF SS OCTA revealed that a large fraction of CVs that form after BRVO are extramacular, and the morphology of CVs varies as a function of retinal location. Depth-resolved study of CVs may offer valuable insights on the pathophysiological mechanisms leading to the development of macular oedema.
Newman NJ, Yu-Wai-Man P, Subramanian PS, Moster ML, Wang A-G, Donahue SP, Leroy BP, Carelli V, Biousse V, Vignal-Clermont C, Sergott RC, Sadun AA, Fernández GR, Chwalisz BK, Banik R, Bazin F, Roux M, Cox ED, Taiel M, Sahel J-A, Sahel J-A. Randomized trial of bilateral gene therapy injection for m.11778G>A MT-ND4 Leber optic neuropathy. Brain 2023;146(4):1328-1341.Abstract
Leber hereditary optic neuropathy (LHON) is an important example of mitochondrial blindness with the m.11778G>A mutation in the MT-ND4 gene being the most common disease-causing mtDNA variant worldwide. The REFLECT phase 3 pivotal study is a randomized, double-masked, placebo-controlled trial investigating the efficacy and safety of bilateral intravitreal injection of lenadogene nolparvovec in patients with a confirmed m.11778G>A mutation, using a recombinant adeno-associated virus vector 2, serotype 2 (rAAV2/2-ND4). The first-affected eye received gene therapy; the fellow (affected/not-yet-affected) eye was randomly injected with gene therapy or placebo. The primary end point was the difference in change from baseline of best-corrected visual acuity (BCVA) in second-affected/not-yet-affected eyes treated with lenadogene nolparvovec versus placebo at 1.5 years post-treatment, expressed in logarithm of the minimal angle of resolution (LogMAR). Forty-eight patients were treated bilaterally and 50 unilaterally. At 1.5 years, the change from baseline in BCVA was not statistically different between second-affected/not-yet-affected eyes receiving lenadogene nolparvovec and placebo (primary end point). A statistically significant improvement in BCVA was reported from baseline to 1.5 years in lenadogene nolparvovec-treated eyes: -0.23 LogMAR for the first-affected eyes of bilaterally treated patients (P < 0.01); and -0.15 LogMAR for second-affected/not-yet-affected eyes of bilaterally treated patients and the first-affected eyes of unilaterally treated patients (P < 0.05). The mean improvement in BCVA from nadir to 1.5 years was -0.38 (0.052) LogMAR and -0.33 (0.052) LogMAR in first-affected and second-affected/not-yet-affected eyes treated with lenadogene nolparvovec, respectively (bilateral treatment group). A mean improvement of -0.33 (0.051) LogMAR and -0.26 (0.051) LogMAR was observed in first-affected lenadogene nolparvovec-treated eyes and second-affected/not-yet-affected placebo-treated eyes, respectively (unilateral treatment group). The proportion of patients with one or both eyes on-chart at 1.5 years was 85.4% and 72.0% for bilaterally and unilaterally treated patients, respectively. The gene therapy was well tolerated, with no systemic issues. Intraocular inflammation, which was mostly mild and well controlled with topical corticosteroids, occurred in 70.7% of lenadogene nolparvovec-treated eyes versus 10.2% of placebo-treated eyes. Among eyes treated with lenadogene nolparvovec, there was no difference in the incidence of intraocular inflammation between bilaterally and unilaterally treated patients. Overall, the REFLECT trial demonstrated an improvement of BCVA in LHON eyes carrying the m.11778G>A mtDNA mutation treated with lenadogene nolparvovec or placebo to a degree not reported in natural history studies and supports an improved benefit/risk profile for bilateral injections of lenadogene nolparvovec relative to unilateral injections.

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