OBJECTIVE: To compare results of simulator-based vs traditional training of medical students in direct ophthalmoscopy. DESIGN: Randomized controlled trial. METHODS: First-year medical student volunteers completed 1 hour of didactic instruction regarding direct oph-thalmoscopes, fundus anatomy, and signs of disease. Students were randomized to an additional hour of training on a direct ophthalmoscope simulator (n = 17) or supervised practice examining classmates (traditional method, n = 16). After 1 week of independent student practice using assigned training methods, masked ophthalmologist observers assessed student ophthalmoscopy skills (technique, efficiency, and global performance) during examination of 5 patient volunteers, using 5-point Likert scales. Students recorded findings and lesion location for each patient. Two masked ophthalmologists graded answer sheets independently using 3-point scales. Students completed surveys before randomization and after assessments. Training groups were compared for grades, observer- and patient-assigned scores, and survey responses. RESULTS: The simulator group reported longer practice times than the traditional group (P =.002). Observers assigned higher technique scores to the simulator group after adjustment for practice time (P =.034). Combined grades (maximum points = 20) were higher for the simulator group (median: 5.0, range: 0.0-11.0) than for the traditional group (median: 4.0, range: 0.0-9.0), although the difference was not significant. The simulator group was less likely to mistake the location of a macular scar in 1 patient (odds ratio: 0.28, 95% confidence interval: 0.056-1.35, P =.013). CONCLUSIONS: Direct ophthalmoscopy is difficult, regardless of training technique, but simulator-based training has apparent advantages, including improved technique, the ability to localize fundus lesions, and a fostering of interest in learning ophthalmoscopy, reflected by increased practice time. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/))

In 1862, the American Journal of Ophthalmology (First Series) commenced monthly publication as the first ophthalmology journal of the United States. With Dr Julius Homberger as Founder and Editor, the journal, which is related to the present American Journal of Ophthalmology in name only, was published monthly until 1884. 1 Straatsma B.R. American Journal of Ophthalmology: Thomas J. Liesegang, MD, appointed Editor-in-Chief. Am J Ophthalmol. 2002; 133 ([editorial]): 819-821 Abstract Full Text Full Text PDF Scopus (4) Google Scholar

The Precision Medicine Initiative gained prominence in the United States when announced in the 2015 State of the Union Address by President Barak Obama.[1] In the following year, the U.S. National Institutes of Health commenced recruitment of 1 million or more people to participate in longitudinal studies to determine the ways in which genomic, health history/behavior, and lifestyle/environmental factors interact to cause disease. Participants in the precision medicine cohort contribute blood samples for genomic analysis and storage, electronic medical records, lifestyle/environmental information, and longitudinal data to a federal “biobank.”[2] This U.S. biobank and other large medical data repositories will be analyzed to reveal previously unknown and unsuspected relationships among genomic findings, health history/behavior, lifestyle/environmental factors, and the risk of or onset of disease. Ophthalmology has been at the forefront of genomic research with discovery of more than 260 genes causing inherited retinal disease and extensive studies of many other eye and vision-related diseases.[3] The several ways in which genomic research affects clinical ophthalmology may be illustrated by considering inherited retinal disease therapy, the important applications of genomic research in ophthalmic oncology, and the major gene-related insights concerning multifactorial diseases such as age-related macular degeneration (AMD). For the inherited retinal disease of Leber congenital amaurosis caused by mutations in both copies of the RPE65 gene, extensive research and favorable 3-year results of a controlled clinical trial of therapy led the U.S. Federal Drug Administration (FDA) to approve treatment with Luxturna (voretigene neparvovec-rzyl; Spark Therapeutics, Inc.).[4] Approved in 2017, this is the first FDA-approved gene therapy for an inherited disease.[345] In patients with RPE65-related Leber congenital amaurosis, early-stage diagnosis and treatment are essential for preservation of vision. Clinical trials for a number of single-gene inherited retinal diseases are in progress, including trials for X-linked retinoschisis, Stargardt disease, Usher syndrome, choroideremia, and retinitis pigmentosa.[5] Investigations using CRISPR systems for genetic modification of inherited retinal disease are underway.[6] In mid-2018, the FDA approved the first “gene-silencing” drug, Onpattro (patisiran; Alnylam Pharmaceuticals, Inc.), for treatment of hereditary transthyretin-mediated amyloidosis.[7] Additional therapies for genomic disease are expected. In ophthalmic oncology, comprehensive knowledge of the genomic alterations responsible for the cancer is the foundation for understanding tumor biology, developing diagnostics, assessing prognosis, and formulating targeted therapeutics.[8910] For ciliochoroidal melanoma, ophthalmic oncologists have, for more than a decade, used genomic studies of tumor biopsy, performed at the time of definitive treatment, to confirm the diagnosis and assess the DNA and RNA factors associated with high risk or low risk of metastasis. Moreover, genetic mutation of BAP1 in the melanoma biopsy may be associated with germline mutation and predisposition for other forms of cancer. Further studies of tumor genomics using genome-wide, single-nucleotide polymorphism mapping arrays have been used to identify significant targets for molecular therapy.[9] In overview, genetic information obtained from the melanoma is combined with tumor pathology, patient family history, medical history/behavior, and lifestyle/environmental factors to assess metastatic risk and provide the best possible care for the patient. For the complex, multifactorial disease of AMD, research has identified approximately 36 causative genetic loci.[10] Although genetic testing is not currently useful for management of patients with AMD, research involving two cohorts totaling 835 persons with two or more AMD risk alleles of CFH or ARMS2 and photographic evidence of early-stage AMD were followed for more than 10 years.[11] Study participants showed AMD progression associated with three modifiable risk factors (smoking, infrequent consumption of fish, and low lutein–zeaxanthin intake). This study illustrates the advantage of research on patients with genetically defined risk factors and comprehensive medical health/behavior and lifestyle/environmental information to demonstrate modifiable factors that may be used in clinical practice to defer progression of disease. Precision medicine recognizes the increasing importance of patient-specific genetics and genomic studies in medical care and the practice of ophthalmology. For ophthalmology, genomics may affect clinical practice in several ways. Patient genomics may lead to a specific diagnosis (e.g., inherited retinal disease) or therapy (e.g., RPE65-related Leber congenital amaurosis) and genomic studies of a tumor (e.g., ciliochoroidal melanoma) provide prognostic information that enables more effective follow-up. Furthermore, research on a genetically defined cohort with a multifactorial disease (e.g., AMD) may lead to discovery of significant treatment options. Adopting the principles of precision medicine, ophthalmologists are encouraged to obtain patient genomic studies when appropriate and to combine genetic information with overall evaluation of family history, health history/behavior, lifestyle/environmental factors, eye health/vision history, and ophthalmology examination. The goal is to determine significant risk factors for disease, enable early-stage diagnosis, and provide the most effective therapy to improve, preserve, and restore vision.

The authors present the multimodal imaging findings of an unusual case of bilateral acquired progressive myelination of the optic disc during a 10-year follow-up period in a hyperopic adolescent patient in the absence of an underlying ocular or systemic abnormality. Myelination of the left optic disc was noted at age 7 and of the right optic disc at age 13, but no other ocular or systemic abnormalities were identified. Cross-sectional optical coherence tomography (OCT) and en face OCT angiography confirmed the presence of myelination of the retinal nerve fiber layer and excluded other etiologic possibilities including an astrocytic hamartoma. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e147-e150.].

Purpose: To report mortality of patients who were eligible for enrollment in the Collaborative Ocular Melanoma Study (COMS) clinical trials of medium-sized choroidal melanoma or large-sized choroidal melanoma but chose to defer treatment or receive no melanoma treatment. Design: Prospective nonrandomized multicenter cohort study as an adjunct to COMS randomized clinical trials. Methods: Patient follow-up procedures included examinations, correspondence, telephone contacts, and National Death Index searches. Primary outcome was patient death measured by all-cause mortality. Secondary outcomes were melanoma treatment and melanoma metastasis. Results: Of 77 patients eligible for COMS clinical trials who chose to defer or receive no melanoma treatment, 61 were appropriate candidates and 45 (74%) enrolled in the natural history study (NHS). In all, 42 patients (42 eyes) had medium melanoma, and the median follow-up was 5.3 years (range, 4-10.7 years). In all, 22 patients (52%) had subsequent melanoma treatment, and 20 (48%) had no melanoma treatment. For the 42 patients, Kaplan-Meier estimate of 5-year mortality was approximately 30% [95% confidence interval (CI), 18%-47%]. For COMS medium melanoma trial, 5-year mortality was 18% (95% CI, 16%-20%), not statistically significantly different from the NHS patients. After adjusting for differences in age and longest basal diameter, the 5-year risk of death for NHS patients versus COMS trial patients was 1.54 (95% CI, 0.93-2.56). Three patients had large melanoma. Melanoma metastasis was confirmed or suspected in 8 (42%) of 19 deaths. Conclusion: Greater mortality and higher risk of death for NHS patients are probative but not conclusive evidence of a beneficial, life-extending effect of medium melanoma treatment.

PURPOSE:To report establishment of the Magrabi ICO Cameroon Eye Institute at Yaoundé, Cameroon, as an ophthalmology subspecialty patient care and training center in Central Africa. DESIGN:Perspective. METHODS:Assessment of unpublished and published material. RESULTS:To improve, preserve and restore eye health and vision in a region with world-high prevalence of functional vision impairment and blindness, the Africa Eye Foundation established the Magrabi ICO Cameroon Eye Institute as an ophthalmology subspecialty patient care center for all in need and a training center for ophthalmologists, ophthalmology subspecialists, and allied personnel. In 2017, the year of its inauguration and the first year of operation, the Magrabi ICO Cameroon Eye Institute provided ophthalmology subspecialty care to more than 25 000 patients and surgery for pediatric and adult cataract, glaucoma, retinal disease, oculoplastic disorders, and other vision-threatening conditions. Outreach programs extended care to an additional 2500 individuals in rural communities and 7 training courses were conducted for ophthalmologists and allied personnel. CONCLUSION:Through ophthalmology subspecialty patient care and the training of ophthalmologists and allied personnel, Magrabi ICO Cameroon Eye Institute is acting to enhance vision and the quality of life for individuals and families in all segments of society.

Purpose: To evaluate visual and surgical outcomes of cataract surgery in eyes with a history of iodine-125 (I-125) brachytherapy for ocular melanoma. Setting: Department of Ophthalmology, David Geffen School of Medicine at UCLA and the Stein Eye Institute, Los Angeles, California, USA. Design: Retrospective case series. Methods: Patients with ocular melanoma treated by I-125 brachytherapy who subsequently had cataract surgery were evaluated. The recorded data included tumor size, location, preoperative ocular comorbidities, corrected distance visual acuity (CDVA), operative complications, and brachytherapy-related maculopathy before and after surgery. Results: Thirty-two eyes of 32 patients were included. The mean age at the time of cataract surgery was 66.1 years. The median follow-up was 53.5 months. There were no intraoperative complications. Eighteen eyes (56.3%) had a history of preoperative radiation retinopathy, 10 involving the macula. Between 2 weeks and 4 weeks postoperatively, 22 eyes (68.8%) had an improvement in CDVA (>= 2 lines). Seven of 10 eyes that failed to improve had radiation maculopathy. By the last follow-up examination, 13 eyes (40.6%) had improved CDVA, 9 eyes (28.1%) were worse (>= 2 lines), and 10 eyes (31.3%) were unchanged (within +/- 1 line). Of 15 eyes that lost CDVA gains achieved between 2 weeks and 4 weeks postoperatively, 9 eyes had new-onset or worsening maculopathy. Cataract surgery had no effect on local tumor control or distant metastasis. Conclusions: Cataract surgery after I-125 brachytherapy for ocular melanoma improved CDVA in most eyes during the immediate postoperative period. Gains were often lost with further followup. Progression of radiation maculopathy was primarily responsible for subsequent visual decline.

PURPOSE:To report the lifetime activities and accomplishments of Jules Stein, MD. DESIGN:Retrospective review. METHODS:Assessment of published and unpublished biographical material. RESULTS:Jules Stein combined his love of music and medicine with organizational skills to achieve successive careers as a musician, an ophthalmologist, an entertainment magnate, and an advocate for vision. To preserve vision, he founded Research to Prevent Blindness, founded the Jules Stein Eye Institute at the University of California, Los Angeles, and led a multiyear campaign to establish the National Eye Institute. CONCLUSIONS:With successive careers and extraordinary achievements, Jules Stein created an enduring legacy of benefits to ophthalmology, vision research, and the prevention of blindness.

In the United States, more than 25 million adults have diabetes, 40% of diabetics have diabetic retinopathy, and diabetes is the leading cause of blindness in people 20 to 74 years of age. Clinical trials have shown that strict control of blood glucose level and other risk factors delays diabetic retinopathy onset, progression, and vision loss. Patients with Type 1 or Type 2 diabetes mellitus, access to an Apple iPhone or iPad, and no psychological or medical condition that would interfere with the study participated in a nonrandomized clinical trial using SightBook™, a free mobile app that enables self-measurement of visual function and creates a password-protected web account for each patient. Sixty patients enrolled in the clinical trial over a 6 month period. Twenty-six participants were men and 34 were women, with ages from 23 to 72 years (mean 45 ± 15) and diabetes duration of 1.5 to 50 years (mean 15.5 ± 11.5). Thirty-nine (65%) patients reported Type 1 diabetes and 21 (35%) patients reported Type 2 diabetes. Every patient established a personal web account on SightBook and invited participation of treating physicians; 51 (85%) patients completed the validated self-reported outcome assessments. Diabetologist examinations of 49 (82%) patients demonstrated systolic hypertension (≥140 mgHg) in 20% and hemoglobin A1c ≥ 7.0% in 56%. Ophthalmology examinations of 45 patients showed visual acuity in the worse-seeing eye of < 20/40 in 18% and diabetic retinopathy in 42% of patients. This clinical trial used a mobile health app to incorporate diabetic patient self-measurement of vision and coordinate the diabetic patient, diabetologist, and ophthalmologist for control of diabetes and diabetic retinopathy risk factors.

OBJECTIVE:To estimate the lifetime attributable risk of cancer associated with whole-body positron emission tomography (PET)/computed tomography (CT) and with CT of the chest, abdomen, and pelvis if performed at various frequencies and for different durations for surveillance of patients with primary choroidal or ciliary body melanoma for distant metastasis.METHODS:Effective radiation doses for whole-body CT and for CT of the chest, abdomen, and pelvis were calculated using Monte Carlo simulation studies. The effective dose of the PET scan was estimated by multiplying fludeoxyglucose F18 radioactivity with dose coefficients. Lifetime attributable risks of cancer were calculated using the approach described in the Biological Effects of Ionizing Radiation VII report.RESULTS:For a 50-year-old patient, an annual CT of the chest, abdomen, and pelvis for 10 years carries an estimated lifetime attributable risk of cancer of 0.9% for male patients and 1.3% for female patients, whereas an annual PET/CT each year for 10 years carries an estimated lifetime attributable risk of cancer of 1.6% for male patients and 1.9% for female patients. Lifetime risk was found to be higher in younger, female patients. The lifetime attributable risk of cancer was estimated to be as high as 7.9% for a 20-year-old female patient receiving a PET/CT scan every 6 months for 10 years.CONCLUSIONS:Aggressive surveillance protocols incorporating CT scanning or PET/CT scanning for detection of metastasis from primary choroidal or ciliary body melanoma appear to confer a significant substantial risk of a secondary malignant tumor in patients who do not succumb to metastatic melanoma within the first few posttreatment years.

PURPOSE:To identify genomic targets for ciliochoroidal melanoma diagnosis, prognosis, and therapy.METHODS:Fifty-eight ciliochoroidal melanomas were analyzed by high-resolution, genome-wide, single nucleotide polymorphism (SNP) mapping arrays. The 58 SNP arrays were compared to 48 HapMap normals representing both sexes and assessed with a systematic statistical method, Genomic Identification of Significant Targets in Cancer (GISTIC), to identify significant ciliochoroidal chromosomal abnormalities including chromosome-arm-sized as well as focal events of amplification and deletion. The 58 SNP arrays were also analyzed to assess copy number.RESULTS:The 58 ciliochoroidal melanomas analyzed by GISTIC showed large regions of chromosome amplification on 6p and 8q in addition to focal amplification peaks on 1q31.3, 4p16.2, 9p23, and 9q33.1. The melanomas also showed large regions of deletion on 1p and all of 3, 6q, 8p, and 16q, as well as focal deletion peaks on 2p12, 2q14.3, 4q26, 5q21.1, 7q21.11, 8p21.3, 9p21.1, 13q21.31, 13q31.3, and 16q23.3. For each large region and focal peak, the statistical significance was computed, and known genes were specified.CONCLUSIONS:High-resolution analysis of ciliochoroidal melanoma cytogenetic aberration patterns supports the utility of systematic characterization of the cancer genome by corroborating known melanoma-related genomic aberrations and identifying additional melanoma-related genomic abnormalities that can be used to identify potential targets for diagnosis, prognosis and therapy.

METHODS. Fifty-eight ciliochoroidal melanomas were analyzed by high-resolution, genome-wide, single nucleotide polymorphism (SNP) mapping arrays. The 58 SNP arrays were compared to 48 HapMap normals representing both sexes and assessed with a systematic statistical method, Genomic Identification of Significant Targets in Cancer (GISTIC), to identify significant ciliochoroidal chromosomal abnormalities including chromosome-arm–sized as well as focal events of amplification and deletion. The 58 SNP arrays were also analyzed to assess copy number.

Editorial Board Steve A. Arshinoff, Dimitri T. Azar Carmen C. Barraquer, William P. D. Chen William V. Good, Chi-Kin Ho, William F. Hoyt Siu-Ping Hui, Son-On Hung, William K. W. Lam Walton W. T. Li, Jeffrey M. Liebmann Calvin C. P. Pang, Gholam A. Peyman David V. Seal, Jack A. Singer Tarun Sharma, Donald T. H. Tan Raymond K. K. Tse, Scheffer C. G. Tseng Donald C. F. Woo, Joseph W. S. Yeung Nancy S. Y. Yuen

OBJECTIVE To report integrative molecular analysis of choroidal melanoma fine-needle aspiration biopsy specimens to identify candidate tumor oncogenes. METHODS Thirty-one choroidal melanoma fine-needle aspiration biopsy specimens were analyzed using cytopathologic diagnosis of melanoma, fluorescence in situ hybridization for chromosome 3, cytogenetic characterization (GeneChip Human 250K NSPI Mapping Arrays; Affymetrix, Santa Clara, California), and gene expression profiles (GeneChip Human Genome U133 Plus 2.0 Arrays, Affymetrix). These analyses were performed by clustering of cytogenetic aberrations, sorting by chromosome 3 loss and chromosome 6p gain, and comparing gene expression profiles in chromosome 3 loss- and chromosome 6p-gain tumors to identify genes with differential expression based on cytogenetic characteristics. RESULTS Of 31 choroidal melanoma biopsy specimens included in this study, 19 tumors had chromosome 3 loss, and 12 tumors without chromosome 3 loss had chromosome 6p gain. Comparative RNA analysis for these 2 groups revealed 49 genes with greater than 4-fold higher expression and 31 genes with greater than 4-fold lower expression in chromosome 3-loss tumors relative to chromosome 6p-gain tumors. CONCLUSIONS Molecular analysis of choroidal melanoma fine-needle aspiration biopsy specimens demonstrated 2 cytogenetically distinct groups characterized by chromosome 3 loss or chromosome 6p gain. In chromosome 3-loss melanomas relative to chromosome 6p-gain melanomas, integrative RNA analysis revealed genes with higher expression and lower expression and identified several genes that have not been reported in previous studies. CLINICAL RELEVANCE Genes differentially expressed between chromosome 3-loss and chromosome 6p-gain melanomas may provide new knowledge about the biologic nature of choroidal melanoma and may contribute to the development of targeted therapies.

Backround Retinal cavernous hemangiomas are rare vascular anomalies, and can be associated with cerebral cavernous malformations (CCM). Distinct mutations have been reported in patients who have both CCMs and retinal cavernous hemangiomas. Methods Fluorescein angiography, spectral domain optical coherence tomography, and genetic testing were performed on a patient with a retinal cavernous hemangioma and a CCM. Results Our patient was heterozygous in the KRIT1/CCM1 gene for a frameshift mutation, c.1088delC. This would be predicted to result in premature protein termination. Discussion We have identified a novel mutation in the KRIT1/CCM1 gene in a patient with both CCM and retinal cavernous hemangioma. We hypothesize that the occurrence of retinal cavernous hemangiomas and CCMs is underlaid by a common mechanism present in the KRIT1/CCM1 gene.

Purpose: To report the ocular response of choroidal melanoma with monosomy 3 vs. disomy 3 after (125)I brachytherapy.Methods and Materials: We evaluated patients with ciliochoroidal melanoma managed with fine needle aspiration biopsy immediately before plaque application for (125)I brachytherapy between January 1, 2005 and December 31, 2008. Patients with (1) cytopathologic diagnosis of melanoma, (2) melanoma chromosome 3 status identified by fluorescence in situ hybridization, and (3) 6 or more months of follow-up after brachytherapy were sorted by monosomy 3 vs. disomy 3 and compared by Kruskal-Wallis test.Results: Among 40 ciliochoroidal melanomas (40 patients), 15 had monosomy 3 and 25 had disomy 3. Monosomy 3 melanomas had a median greatest basal diameter of 12.00 mm and a median tumor thickness of 6.69 mm before brachytherapy; at a median of 1.75 years after brachytherapy, median thickness was 3.10 mm. Median percentage decrease in tumor thickness was 48.3%. Disomy 3 melanomas had a median greatest basal diameter of 10.00 mm and median tumor thickness of 3.19 mm before brachytherapy; at a median of 2.00 years after brachytherapy, median tumor thickness was 2.37 mm. The median percentage decrease in tumor thickness was 22.7%. Monosomy 3 melanomas were statistically greater in size than disomy 3 melanomas (p < 0.001) and showed a greater decrease in tumor thickness after brachytherapy (p = 0.006).Conclusion: In this study, ciliochoroidal melanomas with monosomy 3 were significantly greater in size than disomy 3 melanoma and showed a significantly greater decrease in thickness at a median of 1.75 years after brachytherapy. The greater decrease in monosomy 3 melanoma thickness after brachytherapy is consistent with other malignancies in which more aggressive pathology has been shown to be associated with a greater initial response to radiotherapy. (C) 2011 Elsevier Inc.