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Scelfo C, Mantagos IS. Neurotrophic Keratopathy in Pediatric Patients. Semin Ophthalmol 2021;36(4):289-295.Abstract
Purpose: This review provides an overview of the causes and treatment of neurotrophic keratopathy in the pediatric population.Methods: A thorough review of the current literature discussing neurotrophic keratopathy was conducted then summarized.Results:Fourty-nine papers were reviewed. Congenital and acquired causes of neurotrophic keratopathy exist in the pediatric population. Both medical and surgical approaches to treatment have been trialed, albeit to a limited extent, in pediatric patients. Conservative treatment includes topical lubrication and antibiotics to prevent concurrent infectious ulcer formation. Various neurotrophic factors have been trialed in the form of serum drops to restore corneal sensation when conservative measures fail. Surgically, different corneal neurotization techniques have been developed whereby a donor nerve is routed to the anesthetized cornea to restore innervation and sensation. Conclusions: Advances in the treatment of neurotrophic keratopathy have made corneal reinnervation and restoration of vision more easily attainable in pediatric patients.
Moustafa GA, Borkar DS, Eton EA, Koulisis N, Kloek CE, Kloek CE, Kloek CE. Healthcare disparities contribute to missed follow-up visits after cataract surgery in the USA: results from the perioperative care for intraocular lens study. BMJ Open 2021;11(3):e038565.Abstract
OBJECTIVE: To identify factors that contribute to missed cataract surgery follow-up visits, with an emphasis on socioeconomic and demographic factors. METHODS: In this retrospective cohort study, patients who underwent cataract extraction by phacoemulsification at Massachusetts Eye and Ear between 1 January and 31 December 2014 were reviewed. Second eye cases, remote and international patients, patients with foreign insurance and combined cataract cases were excluded. RESULTS: A total of 1931 cases were reviewed and 1089 cases, corresponding to 3267 scheduled postoperative visits, were included. Of these visits, 157 (4.8%) were missed. Three (0.3%) postoperative day 1, 40 (3.7%) postoperative week 1 and 114 (10.5%) postoperative month 1 visits were missed. Age<30 years (adjusted OR (aOR)=8.2, 95% CI 1.9 to 35.2) and ≥90 years (aOR=5.7, 95% CI 2.0 to 15.6) compared with patients aged 70-79 years, estimated travel time of >2 hours (aOR=3.2, 95% CI 1.4 to 7.4), smokers (aOR=2.7, 95% CI 1.6 to 4.8) and complications identified up to the postoperative visit (aOR=1.4, 95% CI 1.0 to 2.1) predicted a higher rate of missed visits. Ocular comorbidities (aOR=0.7, 95% CI 0.5 to 1.0) and previous visit best-corrected visual acuity (BCVA) of 20/50-20/80 (aOR=0.4, 95% CI 0.3 to 0.7) and 20/90-20/200 (aOR=0.4, 95% CI 0.2 to 0.9), compared with BCVA at the previous visit of 20/40 or better, predicted a lower rate of missed visits. Gender, race/ethnicity, language, education, income, insurance, alcohol use and season of the year were not associated with missed visits. CONCLUSIONS: Medical factors and demographic characteristics, including patient age and distance from the hospital, are associated with missed follow-up visits in cataract surgery. Additional studies are needed to identify disparities in cataract postoperative care that are population-specific. This information can contribute to the implementation of policies and interventions for addressing them.
Norrick A, Esterlechner J, Niebergall-Roth E, Dehio U, Sadeghi S, Schröder HM, Ballikaya S, Stemler N, Ganss C, Dieter K, Dachtler A-K, Merz P, Sel S, Chodosh J, Cursiefen C, Frank NY, Auffarth GU, Ksander B, Frank MH, Kluth MA. Process development and safety evaluation of ABCB5 limbal stem cells as advanced-therapy medicinal product to treat limbal stem cell deficiency. Stem Cell Res Ther 2021;12(1):194.Abstract
BACKGROUND: While therapeutic success of the limbal tissue or cell transplantation to treat severe cases of limbal stem cell (LSC) deficiency (LSCD) strongly depends on the percentage of LSCs within the transplanted cells, prospective LSC enrichment has been hampered by the intranuclear localization of the previously reported LSC marker p63. The recent identification of the ATP-binding cassette transporter ABCB5 as a plasma membrane-spanning marker of LSCs that are capable of restoring the cornea and the development of an antibody directed against an extracellular loop of the ABCB5 molecule stimulated us to develop a novel treatment strategy based on the utilization of in vitro expanded allogeneic ABCB5 LSCs derived from human cadaveric limbal tissue. METHODS: We developed and validated a Good Manufacturing Practice- and European Pharmacopeia-conform production and quality-control process, by which ABCB5 LSCs are derived from human corneal rims, expanded ex vivo, isolated as homogenous cell population, and manufactured as an advanced-therapy medicinal product (ATMP). This product was tested in a preclinical study program investigating the cells' engraftment potential, biodistribution behavior, and safety. RESULTS: ABCB5 LSCs were reliably expanded and manufactured as an ATMP that contains comparably high percentages of cells expressing transcription factors critical for LSC stemness maintenance (p63) and corneal epithelial differentiation (PAX6). Preclinical studies confirmed local engraftment potential of the cells and gave no signals of toxicity and tumorgenicity. These findings were sufficient for the product to be approved by the German Paul Ehrlich Institute and the U.S. Food & Drug Administration to be tested in an international multicenter phase I/IIa clinical trial (NCT03549299) to evaluate the safety and therapeutic efficacy in patients with LSCD. CONCLUSION: Building upon these data in conjunction with the previously shown cornea-restoring capacity of human ABCB5 LSCs in animal models of LSCD, we provide an advanced allogeneic LSC-based treatment strategy that shows promise for replenishment of the patient's LSC pool, recreation of a functional barrier against invading conjunctival cells and restoration of a transparent, avascular cornea.
Jabroun MN, AlWattar BK, Fulton AB. Optical Coherence Tomography Angiography in Prematurity. Semin Ophthalmol 2021;36(4):264-269.Abstract
Purpose: During normal foveal development there is a close interaction between the neurosensory and vascular elements of the fovea making it vulnerable to prematurity and retinopathy of prematurity (ROP). We aim to assess this potential effect on foveal development in preterms evaluated simultaneously with both optical coherence tomography (OCT) and OCT angiography (OCTA).Method: Unrestricted literature search in the PubMed and Cochrane library databases yielded 20 distinct citations. Fifteen were relevant and reviewed.Results: In preterms, OCTA demonstrated a significant decrease in the foveal avascular zone area and an increase in foveal vessel density. OCT showed a decrease in foveal pit depth and an increase in the thickness of the subfoveal retinal layers. Some studies correlated these changes with reduced vision.Conclusion: Changes in the vascular and neurosensory retina were found in premature children. It remains unclear whether this is related to prematurity alone or ROP and its treatment.
Gnanaguru G, Wagschal A, Oh J, Saez-Torres KL, Li T, Temel RE, Kleinman ME, Näär AM, D'Amore PA. Targeting of miR-33 ameliorates phenotypes linked to age-related macular degeneration. Mol Ther 2021;29(7):2281-2293.Abstract
Abnormal cholesterol/lipid homeostasis is linked to neurodegenerative conditions such as age-related macular degeneration (AMD), which is a leading cause of blindness in the elderly. The most prevalent form, termed "dry" AMD, is characterized by pathological cholesterol accumulation beneath the retinal pigment epithelial (RPE) cell layer and inflammation-linked degeneration in the retina. We show here that the cholesterol-regulating microRNA miR-33 was elevated in the RPE of aging mice. Expression of the miR-33 target ATP-binding cassette transporter (ABCA1), a cholesterol efflux pump genetically linked to AMD, declined reciprocally in the RPE with age. In accord, miR-33 modulated ABCA1 expression and cholesterol efflux in human RPE cells. Subcutaneous delivery of miR-33 antisense oligonucleotides (ASO) to aging mice and non-human primates fed a Western-type high fat/cholesterol diet resulted in increased ABCA1 expression, decreased cholesterol accumulation, and reduced immune cell infiltration in the RPE cell layer, accompanied by decreased pathological changes to RPE morphology. These findings suggest that miR-33 targeting may decrease cholesterol deposition and ameliorate AMD initiation and progression.
Böhm MS, Wylegala A, Leon P, Ong Tone S, Ciolino JB, Jurkunas UV. One-Year Clinical Outcomes of Preloaded Descemet Membrane Endothelial Keratoplasty Versus Non-Preloaded Descemet Membrane Endothelial Keratoplasty. Cornea 2021;40(3):311-319.Abstract
PURPOSE: To compare the one-year outcomes of preloaded Descemet membrane endothelial keratoplasty (pDMEK) and non-preloaded DMEK (n-pDMEK) in patients with Fuchs endothelial corneal dystrophy (FECD). METHODS: This retrospective comparative cohort study consecutively included 68 eyes with Fuchs endothelial corneal dystrophy who underwent either pDMEK (n = 38) or n-pDMEK (n = 30) performed by cornea fellows with an experienced surgeon between 2016 and 2018 at the Massachusetts Eye and Ear Infirmary. Exclusion criteria were previous surgery (other than uncomplicated cataract surgery) and any documented evidence of macular or other corneal diseases. Corrected distance visual acuity (CDVA), central corneal thickness, intraocular pressure, patient characteristics, postprocessing endothelial cell count, donor graft data, and complications were compared. RESULTS: CDVA showed similar results for pDMEK (0.12 ± 0.11 logarithm of the minimal angle of resolution [LogMAR]) and n-pDMEK (0.13 ± 0.13 LogMAR) (P = 0.827). Sixty-six percent of the pDMEK eyes and 57% of the n-pDMEK eyes achieved a VA of ≥0.1 LogMAR, and 95% and 97%, respectively, achieved a CDVA ≥0.3 LogMAR. The preoperative central corneal thickness of pDMEK and n-pDMEK (644 ± 62.2 μm, 660.5 ± 56.2 μm) decreased significantly after surgery (525.1 ± 43.6 μm, 526.5 ± 45.2 μm, P < 0.001), with no difference between groups (P = 0.840). The postprocessing endothelial cell count did not differ between pDMEK (2959.2 ± 182.9 cells/mm2) and n-pDMEK (2939.3 ± 278.7 cells/mm2) (P = 0.484). Complication rates were comparable with just the rebubbling performed in a minor procedure room showing a lower rate for pDMEK (13.16%) compared with n-pDMEK (33.33%) (P < 0.045). CONCLUSIONS: One-year clinical outcomes were similar between pDMEK and n-pDMEK procedures, rendering eye bank-prepared pDMEK tissues a useful tool in the treatment of endothelial dysfunction.
Navaratnam J, Salvanos P, Vavvas DG, Bragadóttir R. Ultra-widefield autofluorescence imaging findings in retinoschisis, rhegmatogenous retinal detachment and combined retinoschisis retinal detachment. Acta Ophthalmol 2021;99(2):195-200.Abstract
PURPOSE: Retinoschisis (RS), rhegmatogenous retinal detachment (RRD) and combined RS retinal detachment (RSRD) may resemble clinically and pose a diagnostic challenge. This study investigates the role of the fundus autofluorescence (AF) in differentiating RS, RRD and RSRD. METHODS: Fundus AF changes of 34 eyes diagnosed with RRD, 30 eyes with RS and 12 eyes with RSRD were retrospectively analysed. Ultra-widefield AF (UW-AF) image intensities obtained with the Optomap 200Tx were interpreted as hypo-, hyper- and isoautofluorescent or a mixed pattern with hypo- and hyperautofluorescence over and at the posterior margin (PM) of RRD, RS and RSRD. RESULTS: All RS eyes revealed isoautofluorescence over the area of RS, and nine eyes (30%) showed hypoautofluorescent PM. Among RRD, acute (≤2 weeks) and chronic (>2 weeks) RRD demonstrated distinct AF characteristics. Sixty-two per cent of RRD eyes had acute RRD. From those, 16 eyes (76%) demonstrated hypoautofluorescence over the detached area and 19 (90%) eyes with hyperautofluorescent PM. Sixty-two per cent of chronic RRD eyes demonstrated isoautofluorecence over the detached area. Eight RSRD eyes (67%) revealed hyperautofluorescence in the detached area. The positive predictive value (PPV) for hypoautofluorescence over the area of subretinal fluid (SRF) in RRD was 95%. The PPV for hyperautofluorescence over the area of SRF in RSRD was 100% and for isoautofluorescence for schitic area in RSRD and RS was 76%. CONCLUSION: The UW-AF can be a useful non-invasive adjuvant tool to distinguish between RRD, RS and RSRD. Hypo- or hyperautofluorescence over the area of interest and hyperautofluorescent PM indicates the presence of SRF.
Abbasi B, Rizzo JF. Advances in Neuroscience, Not Devices, Will Determine the Effectiveness of Visual Prostheses. Semin Ophthalmol 2021;36(4):168-175.Abstract
Background: Innovations in engineering and neuroscience have enabled the development of sophisticated visual prosthetic devices. In clinical trials, these devices have provided visual acuities as high as 20/460, enabled coarse navigation, and even allowed for reading of short words. However, long-term commercial viability arguably rests on attaining even better vision and more definitive improvements in tasks of daily living and quality of life. Purpose: Here we review technological and biological obstacles in the implementation of visual prosthetics. Conclusions: Research in the visual prosthetic field has tackled significant technical challenges, including biocompatibility, signal spread through neural tissue, and inadvertent activation of passing axons; however, significant gaps in knowledge remain in the realm of neuroscience, including the neural code of vision and visual plasticity. We assert that further optimization of prosthetic devices alone will not provide markedly improved visual outcomes without significant advances in our understanding of neuroscience.
Rosenblatt TR, Ji MH, Vail D, Ludwig CA, Al-Moujahed A, Pasricha MV, Callaway NF, Kumm J, Moshfeghi DM. Key factors in a rigorous longitudinal image-based assessment of retinopathy of prematurity. Sci Rep 2021;11(1):5369.Abstract
To describe a database of longitudinally graded telemedicine retinal images to be used as a comparator for future studies assessing grader recall bias and ability to detect typical progression (e.g. International Classification of Retinopathy of Prematurity (ICROP) stages) as well as incremental changes in retinopathy of prematurity (ROP). Cohort comprised of retinal images from 84 eyes of 42 patients who were sequentially screened for ROP over 6 consecutive weeks in a telemedicine program and then followed to vascular maturation or treatment, and then disease stabilization. De-identified retinal images across the 6 weekly exams (2520 total images) were graded by an ROP expert based on whether ROP had improved, worsened, or stayed the same compared to the prior week's images, corresponding to an overall clinical "gestalt" score. Subsequently, we examined which parameters might have influenced the examiner's ability to detect longitudinal change; images were graded by the same ROP expert by image view (central, inferior, nasal, superior, temporal) and by retinal components (vascular tortuosity, vascular dilation, stage, hemorrhage, vessel growth), again determining if each particular retinal component or ROP in each image view had improved, worsened, or stayed the same compared to the prior week's images. Agreement between gestalt scores and view, component, and component by view scores was assessed using percent agreement, absolute agreement, and Cohen's weighted kappa statistic to determine if any of the hypothesized image features correlated with the ability to predict ROP disease trajectory in patients. The central view showed substantial agreement with gestalt scores (κ = 0.63), with moderate agreement in the remaining views. Of retinal components, vascular tortuosity showed the most overall agreement with gestalt (κ = 0.42-0.61), with only slight to fair agreement for all other components. This is a well-defined ROP database graded by one expert in a real-world setting in a masked fashion that correlated with the actual (remote in time) exams and known outcomes. This provides a foundation for subsequent study of telemedicine's ability to longitudinally assess ROP disease trajectory, as well as for potential artificial intelligence approaches to retinal image grading, in order to expand patient access to timely, accurate ROP screening.
Costela FM, Reeves SM, Woods RL. An implementation of Bubble Magnification did not improve the video comprehension of individuals with central vision loss. Ophthalmic Physiol Opt 2021;41(4):842-852.Abstract
PURPOSE: People with central vision loss (CVL) watch television, videos and movies, but often report difficulty and have reduced video comprehension. An approach to assist viewing videos is electronic magnification of the video itself, such as Bubble Magnification. METHODS: We created a Bubble Magnification technique that displayed a magnified segment around the centre of interest (COI) as determined by the gaze of participants with normal vision. The 15 participants with CVL viewed video clips shown with 2× and 3× Bubble Magnification, and unedited. We measured video comprehension and gaze coherence. RESULTS: Video comprehension was significantly worse with both 2× (p = 0.01) and 3× Bubble Magnification (p < 0.001) than the unedited video. There was no difference in gaze coherence across conditions (p ≥ 0.58). This was unexpected because we expected a benefit in both video comprehension and gaze coherence. This initial attempt to implement the Bubble Magnification method had flaws that probably reduced its effectiveness. CONCLUSIONS: In the future, we propose alternative implementations of Bubble Magnification, such as variable magnification and bubble size. This study is a first step in the development of an intelligent-magnification approach to providing a vision rehabilitation aid to assist people with CVL.
Nguyen QD, Anesi SD, Chexal S, Chu DS, Dayani PN, Leng T, Meleth AD, Sallam AA, Sheppard JD, Silverstein SM, Toyos M, Wang RC, Foster CS. Management of repository corticotropin injection therapy for non-infectious uveitis: a Delphi study. Acta Ophthalmol 2021;99(6):669-678.Abstract
PURPOSE: Diagnosis and management of non-infectious uveitis (NIU), a major cause of blindness worldwide, are challenging. Corticosteroids, the cornerstone of therapy, are not appropriate for long-term use, and while non-biologic and biologic immunomodulators may be used for some patients, data on their efficacy and safety in this population are limited. Repository corticotropin injection (RCI), believed to affect uveitis by multiple mechanisms, has received regulatory approval for treatment of ophthalmic diseases including posterior uveitis, but is not widely used or discussed in guidelines for the management of uveitis and ocular inflammatory diseases. METHODS: The index study employed a modified Delphi process with a panel of 14 US-based ophthalmologists. Consensus recommendations were developed through a series of three questionnaires. Panellists rated statements on a Likert scale from -5 (strongly disagree) to +5 (strongly agree). RESULTS: The Delphi panel provided consensus recommendations on examinations and testing needed for diagnosis, treatment goals, and the use of corticosteroids, as well as the use of non-biologic and biologic immunomodulators. The panel reached consensus that RCI may be considered for posterior and pan-uveitis, and dosing should be individualized for each patient. Dose reduction/discontinuation should be considered for excessive RCI-related toxicity, hyperglycaemia and/or diabetic complications, excessive costs, or remission ≥ 2 years. Patients should be weaned from RCI if uveitis is stable and well controlled. Adverse events during RCI therapy can be managed by appropriate interventions, with dose reduction/discontinuation considered if events are severe or recurrent. CONCLUSIONS: Expert consensus suggests RCI may be an appropriate treatment option for some patients with uveitis when other therapies are ineffective or intolerable.
Hossain P, Siffel C, Joseph C, Meunier J, Markowitz JT, Dana R. Patient-reported burden of dry eye disease in the UK: a cross-sectional web-based survey. BMJ Open 2021;11(3):e039209.Abstract
OBJECTIVES: To compare sociodemographics and vision-related quality of life (QoL) of individuals with or without dry eye disease (DED); and to explore the impact of DED symptom severity on visual function, activity limitations and work productivity. DESIGN: Cross-sectional web-based survey. SETTING: General UK population. PARTICIPANTS: Adults ≥18 years with (N=1002) or without (N=1003) self-reported DED recruited through email and screened. MAIN OUTCOME MEASURES: All participants completed the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), with six additional questions (items A3-A8), and the EuroQol 5 dimensions 5 levels. DED participants also completed Impact of Dry Eye on Everyday Life questionnaire, 5-item Dry Eye Questionnaire and the Standardised Patient Evaluation of Eye Dryness questionnaire along with the Ocular Comfort Index, Work Productivity and Activity Impairment and the Eye Dryness Score (EDS), a Visual Analogue Scale. RESULTS: Baseline demographic and clinical characteristics were similar in participants with versus without DED (mean age, 55.2 vs 55.0 years; 61.8% vs 61.0% women, respectively) based on recruitment targets. Scores were derived from NEI VFQ-25 using the new 28-item revised VFQ (VFQ-28R) scoring. Mean (SD) VFQ-28R scores were lower in participants with versus without DED, indicating worse functioning (activity limitations, 73.3 (12.3) vs 84.4 (12.3); socioemotional functioning, 75.3 (21.5) vs 90.3 (16.2); total score, 71.6 (12.8) vs 83.6 (12.6)). Higher percentages of problems/inability to do activities were observed among those with versus without DED. The impact of DED on visual function was worse for participants with more severe DED symptoms, as assessed by EDS. In addition, a higher EDS was associated with worse symptoms on common DED scales and a worse impact on work productivity. CONCLUSIONS: DED symptoms were associated with negative effects on visual function, activities and work productivity, whereas worse DED symptoms had a greater impact on vision-related QoL and work productivity.

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