Retinal characteristics in eyes with pathologic myopia among individuals self-identifying as Black.

OBJECTIVE: Investigate retinal characteristics of pathologic myopia (PM) among patients self-identifying as Black. DESIGN: Retrospective cohort single-institution retrospective medical record review. METHODS: Adult patients between January 2005 and December 2014 with International Classification of Diseases (ICD) codes consistent with PM and given 5-year follow-up were evaluated. The Study Group consisted of patients self-identifying as Black, and the Comparison Group consisted of those not self-identifying as Black. Ocular features at study baseline and 5-year follow-up visit were evaluated. RESULTS: Among 428 patients with PM, 60 (14%) self-identified as Black and 18 (30%) had baseline and 5-year follow-up visits. Of the remaining 368 patients, 63 were in the Comparison Group. For the study (n = 18) and Comparison Group (n = 29), median (25th percentile, 75th percentile) baseline visual acuity was 20/40 (20/25, 20/50) and 20/32 (20/25, 20/50) in the better-seeing eye and 20/70 (20/50, 20/1400) and 20/100 (20/50, 20/200), respectively, in the worse-seeing eye. In the eyes that did not have choroidal neovascularization (CNV) in the study and Comparison Group, median study baseline optical coherence tomography central subfield thickness was 196 µm (169, 306 µm) and 225 µm (191, 280 µm), respectively, in the better-seeing eye and 208 µm (181, 260 µm) and 194 µm (171, 248 µm), respectively, in the worse-seeing eye. Baseline prevalence of CNV was 1 Study Group eye (3%) and 20 Comparison Group eyes (34%). By the 5-year visit, zero (0%) and 4 (15%) additional eyes had CNV in the study and Comparison Group, respectively. CONCLUSION: These findings suggest that the prevalence and incidence of CNV may be lower in patients with PM self-identifying as Black when compared with individuals of other races.

PREVALENCE AND PERSISTENCE OF HYPERTRANSMISSION DEFECTS OF VARIOUS SIZES IN EYES WITH INTERMEDIATE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To determine the prevalence and rate of persistence over 2 years of various-sized hypertransmission defects (hyperTDs) in eyes with intermediate age-related macular degeneration. METHODS: Retrospective analysis of optical coherence tomography data from consecutive intermediate age-related macular degeneration patients. Choroidal en face optical coherence tomography images were evaluated for the presence and number of hyperTDs of three different sizes based on greatest linear dimension (small, 63-124 µ m; medium, 125-249 µ m; large, ≥250 µ m) at baseline and at the 2-year follow-up. Interreader agreement was determined by Gwet's agreement coefficient. Disagreements between graders were resolved by the senior investigator to yield a single consensus for all cases. RESULTS: From 273 intermediate age-related macular degeneration eyes (247 patients), 72 and 76 hyperTD lesions were independently identified by two graders at baseline and overall agreement coefficient was 0.89 (95% CI, 0.86-0.93). After adjudication by the senior grader, the final consensus yielded 78 hyperTD lesions from 46 eyes (16.8%) of 42 patients (17.0%) in this study cohort. Among eyes with follow-up optical coherence tomography, 32 of 45 hyperTD lesions (71.1%) persisted. The rates of persistence were 100.0%, 72.7%, and 53.3% in large, medium, and small hyperTD sizes, respectively. CONCLUSION: HyperTDs were present in a significant proportion of intermediate age-related macular degeneration eyes. Acceptable interreader agreement was demonstrated in identifying hyperTD. Larger hyperTD lesions were more likely to persist over 2 years.

Intraocular foreign body: Characteristics, visual outcomes, and predictive values of ocular trauma score.

Introduction: Retained intraocular foreign body (IOFB) remains an important cause of acquired visual impairment. The visual prognosis following treatments for eyes with retained IOFB was observed to be distinct from other mechanisms of open globe injury due to the specific nature and associated circumstances. This study evaluated the risk behaviors, visual results, and predictive values of Ocular Trauma Score (OTS) in determining visual outcomes in patients with IOFB that were not related to terrorism. Methods: Medical records of patients who underwent surgical interventions between January 2015 and December 2020 were retrospectively reviewed. Results: A total of one hundred and sixty-one patients (162 eyes) were recruited. The patients had a mean (standard deviation) age of 47.6 (14.0) years with working male predominance (93.2%). The majority of patients were injured by activities related to grass trimming (63.4%) and metallic objects were the main materials causing injuries (75.7%). Following treatments, the proportion of eyes having vision worse than 20/400 decreased from 126 eyes (77.8%) to 55 eyes (33.9%) at final visit. Ocular trauma score (OTS) had a high potential prediction for final vision in eyes in OTS categories 4 and 5. However, the discordance of final visual acuity distribution was observed in some subgroups of eyes in OTS categories 1 to 3. Conclusion: This study highlights the significance of IOFB related eye injuries in a tertiary care setting. Decision making on treatments should be carefully considered, particularly in eyes in lower OTS categories, in light of a rise in the proportion of patients who experience improved vision after IOFB removal.

Accuracy of Artificial Intelligence in Estimating Best-Corrected Visual Acuity From Fundus Photographs in Eyes With Diabetic Macular Edema.

Importance: Best-corrected visual acuity (BCVA) is a measure used to manage diabetic macular edema (DME), sometimes suggesting development of DME or consideration of initiating, repeating, withholding, or resuming treatment with anti-vascular endothelial growth factor. Using artificial intelligence (AI) to estimate BCVA from fundus images could help clinicians manage DME by reducing the personnel needed for refraction, the time presently required for assessing BCVA, or even the number of office visits if imaged remotely. Objective: To evaluate the potential application of AI techniques for estimating BCVA from fundus photographs with and without ancillary information. Design, Setting, and Participants: Deidentified color fundus images taken after dilation were used post hoc to train AI systems to perform regression from image to BCVA and to evaluate resultant estimation errors. Participants were patients enrolled in the VISTA randomized clinical trial through 148 weeks wherein the study eye was treated with aflibercept or laser. The data from study participants included macular images, clinical information, and BCVA scores by trained examiners following protocol refraction and VA measurement on Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Main Outcomes: Primary outcome was regression evaluated by mean absolute error (MAE); the secondary outcome included percentage of predictions within 10 letters, computed over the entire cohort as well as over subsets categorized by baseline BCVA, determined from baseline through the 148-week visit. Results: Analysis included 7185 macular color fundus images of the study and fellow eyes from 459 participants. Overall, the mean (SD) age was 62.2 (9.8) years, and 250 (54.5%) were male. The baseline BCVA score for the study eyes ranged from 73 to 24 letters (approximate Snellen equivalent 20/40 to 20/320). Using ResNet50 architecture, the MAE for the testing set (n = 641 images) was 9.66 (95% CI, 9.05-10.28); 33% of the values (95% CI, 30%-37%) were within 0 to 5 letters and 28% (95% CI, 25%-32%) within 6 to 10 letters. For BCVA of 100 letters or less but more than 80 letters (20/10 to 20/25, n = 161) and 80 letters or less but more than 55 letters (20/32 to 20/80, n = 309), the MAE was 8.84 letters (95% CI, 7.88-9.81) and 7.91 letters (95% CI, 7.28-8.53), respectively. Conclusions and Relevance: This investigation suggests AI can estimate BCVA directly from fundus photographs in patients with DME, without refraction or subjective visual acuity measurements, often within 1 to 2 lines on an ETDRS chart, supporting this AI concept if additional improvements in estimates can be achieved.

Artificial Intelligence for Diabetic Retinopathy Screening Using Color Retinal Photographs: From Development to Deployment.

Diabetic retinopathy (DR), a leading cause of preventable blindness, is expected to remain a growing health burden worldwide. Screening to detect early sight-threatening lesions of DR can reduce the burden of vision loss; nevertheless, the process requires intensive manual labor and extensive resources to accommodate the increasing number of patients with diabetes. Artificial intelligence (AI) has been shown to be an effective tool which can potentially lower the burden of screening DR and vision loss. In this article, we review the use of AI for DR screening on color retinal photographs in different phases of application, ranging from development to deployment. Early studies of machine learning (ML)-based algorithms using feature extraction to detect DR achieved a high sensitivity but relatively lower specificity. Robust sensitivity and specificity were achieved with the application of deep learning (DL), although ML is still used in some tasks. Public datasets were utilized in retrospective validations of the developmental phases in most algorithms, which require a large number of photographs. Large prospective clinical validation studies led to the approval of DL for autonomous screening of DR although the semi-autonomous approach may be preferable in some real-world settings. There have been few reports on real-world implementations of DL for DR screening. It is possible that AI may improve some real-world indicators for eye care in DR, such as increased screening uptake and referral adherence, but this has not been proven. The challenges in deployment may include workflow issues, such as mydriasis to lower ungradable cases; technical issues, such as integration into electronic health record systems and integration into existing camera systems; ethical issues, such as data privacy and security; acceptance of personnel and patients; and health-economic issues, such as the need to conduct health economic evaluations of using AI in the context of the country. The deployment of AI for DR screening should follow the governance model for AI in healthcare which outlines four main components: fairness, transparency, trustworthiness, and accountability.

Open Globe Injury in a Tertiary Hospital of Northern Thailand: No Vision Survival and Ocular Trauma Score.

Purpose: To determine characteristics and factors associated with no vision survival (included no light perception, enucleation, and evisceration) following open globe injury (OGI) and to correlate the proportion of final vision to predictive values of ocular trauma score (OTS). Patients and Methods: The medical records of consecutive patients diagnosed as OGI between January 2015 and December 2020 were retrospectively reviewed. Data collected included demographics, mechanisms and modes of injuries, ophthalmic presentations, managements, and visual outcomes at the final visit. Results: Three hundred and seventy-one patients with a mean (standard deviation, SD) age of 44.0 (17.4) years were included. Male with workplace injury was the most frequent scenario. High-velocity metallic objects were the predominant causative materials. Following treatments, fifty-six eyes (14.9%) obtained no vision survival. Factors associated with no vision survival following OGI were low presenting vision, globe perforation, larger wound, presence of relative afferent pupillary defect, retinal detachment, and vitreous hemorrhage. Compared to OTS predictive values, eyes in OTS categories 1 and 2 had a lower proportion of no vision survival. Conclusion: This study identified the importance of workplace injuries. Overall, there were comparable final visions between OTS and this study. However, a reduced proportion of no vision survival among severely injured eyes signifies the challenges of OGI management.

Ophthalmic imaging in diabetic retinopathy: A review.

Retinal imaging has been a key tool in the diagnosis, evaluation, management and documentation of diabetic retinopathy (DR) and diabetic macular oedema (DMO) for many decades. Imaging technologies have rapidly evolved over the last few decades, yielding images with higher resolution and contrast with less time, effort and invasiveness. While many retinal imaging technologies provide detailed insight into retinal structure such as colour reflectance photography and optical coherence tomography (OCT), others such as fluorescein or OCT angiography and oximetry provide dynamic and functional information. Many other novel imaging technologies are in development and are poised to further enhance our evaluation of patients with DR.

Correlation between change in central subfield thickness and change in visual acuity in macular edema due to retinal vein occlusion: post hoc analysis of COPERNICUS, GALILEO, and VIBRANT.

PURPOSE: Assess correlation between change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in eyes with macular edema due to retinal vein occlusion (RVO) that received intravitreal aflibercept injections (IAI). METHODS: Post hoc analysis of COPERNICUS and GALILEO trials for CRVO and VIBRANT trial for BRVO with relationships determined using Pearson correlation coefficient. RESULTS: In COPERNICUS, correlations (r) between change in CST and change in BCVA from baseline at weeks 12, 24, 52, and 100 were -0.36 (95% CI: -0.52, -0.18; P < 0.001), -0.38 (95% CI: -0.53, -0.20; P < 0.001), -0.44 (95% CI: -0.58, -0.27; P < 0.001), and -0.41 (95% CI: -0.56, -0.23; P < 0.001), respectively. CST changes accounted for only 21% of the variance in BCVA changes; every 100-µm decrease in CST was associated with a 2.1-letter increase in BCVA (P = 0.003). Similar findings were noted for GALILEO (r, -0.45 to -0.23) and VIBRANT (r, -0.36 to -0.32) trials. CONCLUSION: In eyes treated with IAI for macular edema due to RVO, correlation between change in CST and change in BCVA was weak to moderate. While change in CST may be helpful in determining the need for anti-VEGF therapy, these findings do not support using changes in CST as a surrogate for changes in visual acuity outcomes.

New frontiers of retinal therapeutic intervention: a critical analysis of novel approaches.

A recent wave of pharmacologic and technologic innovations has revolutionized our management of retinal diseases. Many of these advancements have demonstrated efficacy and can increase the quality of life while potentially reducing complications and decreasing the burden of care for patients. Some advances, such as longer-acting anti-vascular endothelial growth factor agents, port delivery systems, gene therapy, and retinal prosthetics have been approved by the US Food and Drug Administration, and are available for clinical use. Countless other therapeutics are in various stages of development, promising a bright future for further improvements in the management of the retinal disease. Herein, we have highlighted several important novel therapies and therapeutic approaches and examine the opportunities and limitations offered by these innovations at the new frontier. KEY MESSAGESNumerous pharmacologic and technologic advancements have been emerging, providing a higher treatment efficacy while decreasing the burden and associated side effects.Anti-vascular endothelial growth factor (anti-VEGF) and its longer-acting agents have dramatically improved visual outcomes and have become a mainstay treatment in various retinal diseases.Gene therapy and retinal prosthesis implantation in the treatment of congenital retinal dystrophy can accomplish the partial restoration of vision and improved daily function in patients with blindness, an unprecedented success in the field of retina.

Correlation of Change in Central Subfield Thickness and Change in Visual Acuity in Neovascular AMD: Post Hoc Analysis of VIEW 1 and 2.

PURPOSE: Determine correlation between change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in neovascular age-related macular degeneration receiving anti-vascular endothelial growth factor agents. DESIGN: A post hoc analysis of VIEW 1 and 2 randomized clinical trials. METHODS: This analysis included participants randomized to ranibizumab 0.5 mg every 4 weeks (Rq4), intravitreal aflibercept injection 2 mg every 4 weeks (2q4), and intravitreal aflibercept injection 2 mg every 8 weeks after 3 monthly doses (2q8) to week 52, followed by capped as-needed (at least every 12 weeks) dosing to week 96. Relationship between changes in CST and BCVA was determined using Pearson correlation coefficient. RESULTS: Of 1815 eyes, 595 were assigned to the Rq4, 613 to 2q4, and 607 to 2q8 arms. Correlations (95% confidence intervals [CI]) at weeks 12, 52, and 96 were -0.08 (95% CI, -0.17 to 0.00), -0.05 (95% CI, -0.14 to 0.04), and -0.15 (95% CI, -0.24 to -0.06) for Rq4; -0.13 (95% CI, -0.21 to -0.04), -0.06 (95% CI, -0.14 to 0.03) and -0.04 (95% CI, -0.13 to 0.05) for 2q4, and -0.04 (95% CI, -0.12 to 0.05), -0.01 (95% CI, -0.09 to 0.08), and -0.01 (95% CI, -0.10 to 0.09) for 2q8. Linear regression analysis adjusted for relevant baseline factors showed CST changes accounted for 11% of BCVA changes. Every 100 µm decrease in CST was associated with a 0.3 letter decrease (P = .25) at week 52 and a 0.14 letter decrease (P = .69) at week 96. CONCLUSIONS: Weak or no correlation was found between changes in CST and BCVA with either agent or regimen, suggesting changes in CST should not be used as a surrogate for visual acuity outcomes in neovascular age-related macular degeneration.

Correlation of Change in Macular Thickness With Change in Visual Acuity in Diabetic Macular Edema: Post Hoc Analysis of VISTA and VIVID Trials.

Purpose: To assess the correlation between the change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in eyes with diabetic macular edema (DME) treated with fixed-dosing intravitreal aflibercept injection (IAI). Methods: This post hoc analysis of the VISTA and VIVID randomized controlled clinical trials, in which 862 eyes with central-involved DME were randomly assigned to IAI 2 mg every 4 weeks (2q4; 290 eyes), IAI 2 mg every 8 weeks after 5 initial monthly doses (2q8; 286 eyes), or macular laser (286 eyes) and followed through 100 weeks. Correlations between the change in CST and change in BCVA from baseline to weeks 12, 52, and 100 were assessed using the Pearson correlation. Results: The respective correlations (r [95% CI]) at weeks 12, 52, and 100 were -0.39 (-0.49 to -0.29), -0.27 (-0.38 to -0.15), and -0.30 (-0.41 to -0.17) in the 2q4 arm and -0.28 (-0.39 to -0.17), -0.29 (-0.41 to -0.17), and -0.33 (-0.44 to -0.20) in the 2q8 arm. Linear regression analysis of the correlation at week 100, adjusted for relevant baseline factors, showed CST changes accounted for 17% of the variance in BCVA changes; every 100-µm decrease in CST was associated with a 1.2-letter increase in BCVA (P = .001). Conclusions: Correlations between the change in CST and change in BCVA after 2q4 or 2q8 fixed-dosing IAI for DME were modest. Although a change in CST might be important in determining the need for antivascular endothelial growth factor for DME at follow-up, it was not a good surrogate for VA outcomes.

Prevention of vision-threatening complications in diabetic retinopathy: two perspectives based on results from the DRCR Retina Network Protocol W and the Regeneron-sponsored PANORAMA.

PURPOSE OF REVIEW: The use of intravitreous antivascular endothelial growth factor to prevent center-involved diabetic macular edema (CI-DME) with vision loss and proliferative diabetic retinopathy (PDR) has been investigated and recently reported in two randomized clinical trials. Although both trials showed substantial superiority of aflibercept at preventing the development of vision-threatening complications (VTCs) of CI-DME or PDR compared with sham at 1 or 2 years, without a concomitant benefit in visual acuity outcomes, the interpretation of the results and its application to clinical practice resulted in two disparate opinions. In this review, we discuss these two trials including their similarities and differences, other relevant studies, and considerations regarding the interpretation and the application of these results into clinical practice. RECENT FINDINGS: The Diabetic Retinopathy Clinical Research Retina Network Protocol W and the PANORAMA study demonstrated significantly lower probabilities of developing CI-DME or PDR at 2 years with intravitreous aflibercept compared with sham in eyes with moderate (Protocol W) or moderately severe (PANORAMA) to severe non-PDR (NPDR). However, visual acuity outcomes were not different. SUMMARY: Although intravitreous aflibercept injections reduce the risk of VTCs in eyes with moderate-to-severe NPDR, the absence of visual acuity benefits supports the need for four-year results.

Clinic-Based Eye Disease Screening Using Non-Expert Fundus Photo Graders at the Point of Screening: Diagnostic Validity and Yield.

PURPOSE: The intent of this study was to determine the diagnostic accuracy of several diagnostic tests for age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, and cataract, as well as the proportions of patients with eye disease from each of 3 enrolling clinics. DESIGN: Diagnostic accuracy study. METHODS: Patients ≥50 years old in a diabetes, thyroid, and general medicine clinic were screened using visual acuity, tonometry, and fundus photography. Photographs were graded at the point-of-screening by non-ophthalmic personnel. Participants with positive screening test results in either eye and a 10% random sample with negative results in both eyes were referred for an in-person, reference-standard ophthalmology examination. RESULTS: Of 889 participants enrolled, 229 participants failed at least 1 test in either eye, of which 189 presented for an ophthalmic examination. An additional 76 participants with completely normal screening test results were referred for examination, of which 50 attended. Fundus photography screening had the highest yield for DR (sensitivity: 67%; 95% confidence interval [CI]: 39%-87%), visual acuity screening for cataract (sensitivity: 89%; 95% CI: 86%-92%), and intraocular pressure screening for glaucoma or suspected glaucoma (sensitivity: 25%; 95% CI: 14%-40%). The burden of disease was relatively high in all 3 clinics, with at least 1 of the diseases of interest (ie, AMD, DR, glaucoma or suspected glaucoma, or cataract) detected in 25% of participants (95% CI: 17-35%) from the diabeteses clinic, 34% (95% CI: 22%-49%) from the thyroid clinic, and 21% (95% CI: 13%-32%) from the general clinic. CONCLUSIONS: Non-expert eye disease screening in health clinics may be a useful model for detection of eye disease in resource-limited settings.

Contralateral Eye Involvement and Retinal Detachment in Patients with Cytomegalovirus Retinitis Treated with Intravitreous Ganciclovir.

Purpose: To determine the incidence of contralateral eye involvement and retinal detachment in HIV-infected patients with cytomegalovirus retinitis treated with repeated intravitreous ganciclovir.Methods: In a prospective cohort study in Northern Thailand, HIV-infected patients with cytomegalovirus retinitis were treated with antiretroviral therapy and intravitreous ganciclovir injections and followed for 3 months for contralateral cytomegalovirus retinitis and retinal detachment.Results: Of 49 participants with unilateral cytomegalovirus retinitis at enrollment, 7 developed contralateral eye involvement (4.8/100 person-months, 95% CI 1.9-9.8). Of 105 eyes without a retinal detachment at enrollment, 6 developed a retinal detachment (2.0/100 eye-months, 95% CI 0.7-4.3). Baseline clinical factors were not associated with the development of either outcome.Conclusion: Eyes treated with intravitreous ganciclovir experienced retinal detachment at a rate similar to other populations treated with systemic antivirals. The risk of contralateral eye involvement was relatively high during the first 3 months after initial diagnosis despite the institution of antiretroviral therapy.

Repeatability and Agreement of Visual Acuity Using the ETDRS Number Chart, Landolt C Chart, or ETDRS Alphabet Chart in Eyes With or Without Sight-Threatening Diseases.

Importance: The Early Treatment Diabetic Retinopathy Study (ETDRS) alphabet chart is not feasible for measuring best-corrected visual acuity (BCVA) for individuals who are unfamiliar with the Roman alphabet. The ETDRS Landolt C chart is an alternative, but it may not reflect true BCVA among those with confusion between left and right. The ETDRS number chart might overcome these limitations, but little is known regarding its reliability. Objective: To evaluate repeatability and agreement of BCVA using the ETDRS number chart or Landolt C chart compared with ETDRS alphabet charts in healthy and diseased eyes. Design, Setting, and Participants: A cross-sectional study was conducted in Thailand from July 1, 2015, to June 30, 2016, among 154 adult Thai individuals. Those who could read Roman alphabets were classified into the following 4 groups, using 1 eye per participant: group A, which comprised 60 healthy eyes (BCVA, 20/20-20/25); group B, which comprised 40 eyes with age-related cataract, diabetic macular edema, or age-related macular degeneration (BCVA, 20/20-20/40); group C, which comprised 40 eyes with age-related cataract, diabetic macular edema, or age-related macular degeneration (BCVA, 20/50-20/100); and group D, which comprised 14 eyes with age-related cataract, diabetic macular edema, or age-related macular degeneration (BCVA, 20/125-20/200). Interventions: Two standardized 4-m BCVA measurements with 3 different Precision Vision ETDRS charts (PV number, Landolt C, and alphabet), in random sequence, performed 30 minutes apart. Main Outcomes and Measures: Repeatability, agreement, and testing duration of BCVA. Results: Of 154 Thai participants (82 women and 72 men; mean [SD] age, 52.9 [18.2] years), the ETDRS number chart had strong repeatability coefficients (group A, 0.61 [95% CI, 0.42-0.75]; group B, 0.87 [95% CI, 0.78-0.93]; group C, 0.81 [95% CI, 0.67-0.90]; and group D, 0.81 [95% CI, 0.49-0.94]). Concordance correlation coefficients between the number and alphabet charts were also strong (group A, 0.89 [95% CI, 0.82-0.93]; group B, 0.97 [95% CI, 0.94-0.98]; group C, 0.92 [95% CI, 0.86-0.96]; and group D, 0.96 [95% CI, 0.87-0.99]), while the concordance correlation coefficients between the Landolt C and alphabet charts were lower (group A, 0.72 [95% CI, 0.52-0.83]; group B, 0.83 [95% CI, 0.68-0.91]; group C, 0.79 [95% CI, 0.61-0.89]; and group D, 0.89 [95% CI, 0.66-0.97]). The mean letter score difference between the number and alphabet charts was 1 (95% limits of agreement, -4 to +6) compared with -7 (95% limits of agreement, -18 to +5; P < .001) between the Landolt C and alphabet charts. Conclusions and Relevance: The repeatability coefficients and concordance correlation coefficients suggest that ETDRS number charts are viable for measuring BCVA in clinical practice and trials for individuals who are unfamiliar with the Roman alphabet.