Jules Stein, MD: Ophthalmologist, Entertainment Magnate, and Advocate for Vision.

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 METHODS: Assessment of published and unpublished biographical material.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.

Prospective, Randomized Trial Comparing Simulator-based versus Traditional Teaching of Direct Ophthalmoscopy for Medical Students.

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 ophthalmoscopes, 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.

Novel KRIT1/CCM1 mutation in a patient with retinal cavernous hemangioma and cerebral cavernous malformation.

BACKGROUND: 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.

Reactions to and desire for prognostic testing in choroidal melanoma patients.

To determine if choroidal melanoma patients want cytogenetic prognostic information. Ninety-nine choroidal melanoma patients completed a questionnaire regarding their opinions about receiving prognostic information. The perceived usefulness of prognostic information was evaluated in patients who had undergone cytogenetic testing. Depressive symptoms, quality of life, and interest in supportive counseling during test receipt were assessed. Ninety-seven percent of respondents reported that they would have wanted prognostic information at the time of their treatment and 98% of respondents reported that supportive counseling should be offered when prognostic information is given. Patients who had received a more favorable prognostic result were more likely to endorse the usefulness of cytogenetic testing than were patients who had received a less favorable prognostic result. Psychological status did not vary significantly as a function of cytogenetic test result. Prognostic information was important to patients with choroidal melanoma, even in the absence of prophylactic measures which might improve prognosis.

Magrabi ICO Cameroon Eye Institute, Yaoundé, Cameroon: Ophthalmology Subspecialty Patient Care and Training Center in Central Africa.

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.

Detailed analysis of immunologic effects of the cytotoxic T lymphocyte-associated antigen 4-blocking monoclonal antibody tremelimumab in peripheral blood of patients with melanoma.

BACKGROUND: CTLA4-blocking antibodies induce tumor regression in a subset of patients with melanoma. Analysis of immune parameters in peripheral blood may help define how responses are mediated. METHODS: Peripheral blood from HLA-A*0201-positive patients with advanced melanoma receiving tremelimumab (formerly CP-675,206) at 10 mg/kg monthly was repeatedly sampled during the first 4 cycles. Samples were analyzed by 1) tetramer and ELISPOT assays for reactivity to CMV, EBV, MART1, gp100, and tyrosinase; 2) activation HLA-DR and memory CD45RO markers on CD4+/CD8+ cells; and 3) real-time quantitative PCR of mRNA for FoxP3 transcription factor, preferentially expressed by T regulatory cells. The primary endpoint was difference in MART1-specific T cells by tetramer assay. Immunological data were explored for significant trends using clustering analysis. RESULTS: Three of 12 patients eligible for immune monitoring had tumor regression lasting > 2 years without relapse. There was no significant change in percent of MART1-specific T cells by tetramer assay. Additionally, there was no generalized trend toward postdosing changes in other antigen-specific CD8+ cell populations, FoxP3 transcripts, or overall changes in surface expression of T-cell activation or memory markers. Unsupervised hierarchical clustering based on immune monitoring data segregated patients randomly. However, clustering according to T-cell activation or memory markers separated patients with clinical response and most patients with inflammatory toxicity into a common subgroup. CONCLUSION: Administration of CTLA4-blocking antibody tremelimumab to patients with advanced melanoma results in a subset of patients with long-lived tumor responses. T-cell activation and memory markers served as the only readout of the pharmacodynamic effects of this antibody in peripheral blood. CLINICAL TRIAL REGISTRATION NUMBER: NCT00086489.

Baseline echographic characteristics of tumors in eyes of patients enrolled in the Collaborative Ocular Melanoma Study: COMS report no. 29.

PURPOSE: To report baseline echographic characteristics of tumors in patients enrolled in the Collaborative Ocular Melanoma Study (COMS) randomized trials, to determine how often these characteristics matched prespecified criteria for choroidal melanoma, to explore associations between echographic variables, and to compare specific echographic characteristics with pathologic characteristics of tumors in enucleated eyes. DESIGN: Retrospective analyses of baseline data from multicenter randomized clinical trials. PARTICIPANTS: Patients enrolled in the COMS large trial or medium tumor trials (N = 2320). METHODS: Standardized echography was used to document selected characteristics of tumors at baseline. Criteria were established to assess the consistency of echographic features with the diagnosis of melanoma. For eyes assigned to enucleation, the echographic diagnosis and evaluation for extraocular extension by the Echography Center were compared with gradings made by the Pathology Center and Pathology Review Committee. MAIN OUTCOME MEASURES: Presence of various echographic and pathologic characteristics. RESULTS: Two thousand forty-three tumors (88%) exhibited low to medium reflectivity (n = 1409), a mushroom shape (n = 101), or both (n = 533). Tumors with apical height > 10 mm were more likely (P<0.001) to have a mushroom shape and less likely to have a posterior location (P<0.001) than less elevated tumors. One thousand five hundred fifty-nine (99.7%) of 1563 tumors judged by echography to be consistent with the diagnosis of melanoma were confirmed by pathology to be choroidal melanoma. For measurable extrascleral tumors < 1.5 mm in height by pathology, the Echography Center graders judged extrascleral extension as possibly present in only 1 of 16 (6%) tumors, compared with 57% (4/7) of eyes with extrascleral extension measuring > or = 1.5 mm in height. CONCLUSIONS: Eighty-eight percent of the tumors in the COMS exhibited features characteristic for melanoma: low to medium reflectivity, the classic mushroom shape, or both. Using additional preset criteria, 96% of tumors exhibited baseline echographic characteristics consistent with the diagnosis of melanoma. Echography graders were able to detect extrascleral nodules > or = 1.5 mm in elevation but not minimally elevated extraocular tumor extension. Clinicians and echographers can use these data to improve their understanding of the echographic features of untreated uveal melanomas.

Transscleral fine-needle aspiration biopsy of macular choroidal melanoma.

PURPOSE: To report transscleral 30-gauge fine-needle aspiration biopsy (FNAB) for cytology and cytogenetics in eyes with macular choroidal melanoma. DESIGN: Prospective, interventional case series. METHODS: Twenty-five patients (25 eyes) who underwent transscleral 30-gauge FNAB of macular choroidal melanoma immediately prior to iodine-125 plaque placement were included in this study, conducted at a tertiary care university hospital. The main outcome measures were FNAB feasibility, cytology, cytogenetic analysis for monosomy 3, and surgical complications. RESULTS: Transscleral 30-gauge FNAB of choroidal melanoma in the macula was performed in 24 of 25 (96%) eyes and was not feasible owing to insufficient exposure in one eye (4%). Biopsy was diagnostic of choroidal melanoma in 17 of 24 (71%) eyes. Fluorescent in situ hybridization (FISH) and/or GeneChip 500k NspI Mapping array (Affymetrix, Santa Clara, California, USA) analysis for monosomy 3 was completed in 16 of 24 (67%) revealing monosomy 3 in five eyes and disomy 3 in 11 eyes. Retinal perforation (four eyes) did not require treatment or result in retinal detachment; submacular hemorrhage (nine eyes) and vitreous hemorrhage (five eyes) cleared spontaneously within one month. CONCLUSION: Transscleral FNAB of macular choroidal melanoma is feasible in most eyes and frequently yields cytogenetic information relevant to prognosis.

Mortality after deferral of treatment or no treatment for choroidal melanoma.

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.

Bilateral Acquired Progressive Retinal Nerve Fiber Layer Myelination.

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.].

Outcomes of cataract surgery in eyes with ocular melanoma treated with iodine-125 brachytherapy.

PURPOSE: To evaluate visual and surgical outcomes of cataract surgery in eyes with a history of iodine-125 (I125) 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 I125 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 I125 brachytherapy for ocular melanoma improved CDVA in most eyes during the immediate postoperative period. Gains were often lost with further follow-up. Progression of radiation maculopathy was primarily responsible for subsequent visual decline.

High-density genome array is superior to fluorescence in-situ hybridization analysis of monosomy 3 in choroidal melanoma fine needle aspiration biopsy.

PURPOSE: Using fluorescence in situ hybridization (FISH) and high-density single nucleotide polymorphism (SNP) mapping genome array, we comparatively evaluated chromosome 3 status and other chromosomal aberrations within a series of choroidal melanomas biopsied by fine needle aspiration (FNAB). METHODS: Transscleral FNAB was performed in 59 patients (59 eyes) who had a clinical diagnosis of choroidal melanoma. Biopsies were processed for chromosome 3 status by centromeric interphase FISH, cytopathology, cell culture, and simultaneous genomic DNA and RNA mapping array analysis. RESULTS: FISH yielded chromosome 3 status in 38 of 59 (64%) eyes, while high-density SNP mapping array yielded chromosome 3 status in 43 of 59 (73%) eyes. Monosomy 3 was detected by FISH in 15 of 38 (39%) cases, and high-density SNP mapping array data confirmed the finding in 13 of the 15 cases. Furthermore, high-density SNP mapping array revealed five additional cases of significant chromosome 3 aberration not detected by FISH. High-density genomic mapping also provided detailed patterns of chromosomal gain and loss on chromosomes 1, 6, 8, and 9 which segregated into two groups characterized by either monosomy 3 or chromosome 6p gain. CONCLUSIONS: High-density SNP mapping array was better than FISH in detecting chromosome 3 aberrations and monosomy in our melanoma samples. More importantly, the mapping arrays detected additional patterns of chromosomal aberration, which suggest specific pathways for cytogenetic rearrangements in choroidal melanoma and may improve prognostic testing.

Fluorescent in situ hybridization for monosomy 3 via 30-gauge fine-needle aspiration biopsy of choroidal melanoma in vivo.

OBJECTIVE: To report the feasibility of intraoperative transscleral fine-needle aspiration biopsy at plaque surgery to obtain cells for monosomy 3 analysis in patients with choroidal melanoma. DESIGN: Consecutive interventional case series. PARTICIPANTS: Eighteen patients (18 eyes) with choroidal melanoma who had fine-needle aspiration biopsy performed with a 30-gauge needle at time of iodine 125 plaque placement. INTERVENTION: Cytology and cytogenetic analysis for monosomy 3 were obtained from biopsy specimens. MAIN OUTCOME MEASURES: Cytology, cytogenetic analysis for monosomy 3, and complications and feasibility of transscleral fine-needle aspiration biopsy of choroidal melanoma in vivo. RESULTS: Fine-needle aspiration biopsy was diagnostic of choroidal melanoma in 14 of 18 cases and resulted in viable cell cultures for fluorescent in situ hybridization (FISH) analysis in 9 cases. Fluorescent in situ hybridization for monosomy 3 was positive in 4 of the 9 cases. One patient had a mild vitreous hemorrhage. Tumors between 2 and 3 mm in height and those that yielded cells that did not attach in culture were most likely to have insufficient growth for FISH analysis. CONCLUSIONS: Transscleral fine-needle aspiration biopsy and FISH for monosomy 3 may provide important prognostic information on patients who undergo plaque radiotherapy for choroidal melanoma.

Surveillance of the eye and vision in clinical trials of CP-675,206 for metastatic melanoma.

PURPOSE: To determine the ocular safety of CP-675,206 (Pfizer, New York, New York, USA), a fully human anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody in clinical trials of immunotherapy of metastatic melanoma. DESIGN: Prospective, nonrandomized study of the eye and vision in phase I/II clinical trials of CP-675,206 in metastatic melanoma conducted at the University of California, Los Angeles. METHODS: Patients with regional or distant metastatic melanoma were enrolled in phase I/II clinical trials evaluating the safety and antitumor efficacy of CP-675,206 alone or in combination with melanoma antigen peptide-pulsed dendritic cell vaccines. Ophthalmic evaluation was performed at the onset of CP-675,206 immunotherapy (baseline evaluation), two months or more after the onset of CP-675,206 immunotherapy (end-study evaluation), and at two- to three-month intervals thereafter in patients who continued to receive CP-675,206 immunotherapy (poststudy evaluation). Baseline and end-study evaluations included comprehensive ophthalmic examination, psychophysical and electrophysiologic visual function assessment, fundus photography, fluorescein angiography, and visual function assessment. RESULTS: Twenty patients with metastatic melanoma arising from the skin, mucosa, eye, or unknown site were evaluated. Systemic toxicity attributed to CP-675,206 included dermatologic manifestations, diarrhea, and autoimmune hepatitis with panhypopituitarism. A subset of patients receiving CP-675,206 demonstrated antitumor efficacy with partial response or complete response of metastatic melanoma. Comparison of ophthalmic baseline with end-study evaluations in all 20 patients and limited-term poststudy evaluations showed no adverse effect of CP-675,206 immunotherapy on the eye or vision. CONCLUSIONS: In this study, CP-675,206 immunotherapy for metastatic melanoma did not adversely affect the eye or vision.

Iris and anterior chamber angle neovascularization after iodine 125 brachytherapy for uveal melanoma.

PURPOSE: Iris neovascularization (INV) and anterior chamber angle neovascularization after radiotherapy for uveal melanoma may lead to neovascular glaucoma and enucleation. However, neovascularization of the anterior ocular segment may respond favorably to treatment with panretinal photocoagulation. The purpose of this study was to evaluate the frequency, interval to development, and predisposing factors of anterior ocular segment neovascularization following iodine 125 (I125) brachytherapy for uveal melanoma. DESIGN: Retrospective, interventional, consecutive case series. PARTICIPANTS: Sixty-five patients (65 eyes), consecutively treated with I125 brachytherapy for uveal melanoma from 1995 through 2000 and followed up after radiation therapy for 24 months or more. METHODS: Clinical findings and ultrasonography characteristics as well as treatment parameters were analyzed. MAIN OUTCOME MEASURES: The frequency of INV was determined and the interval to development of INV as well as the predisposing factors were analyzed statistically. RESULTS: In 15 of 65 eyes (23%), INV was detected after I125 brachytherapy at a mean +/- standard deviation of 26.66+/-11.63 months (median, 24 months; range, 9-48 months). Risk factors displaying the stronger correlation with INV were greater maximal tumor height (P<0.01), greater tumor vascularity (P<0.01), and disinsertion of horizontal rectus muscles (P = 0.01). CONCLUSIONS: After I125 brachytherapy for choroidal melanoma, INV developed in 23% of eyes and was correlated with larger tumor size, greater tumor vascularity, and disinsertion of a horizontal rectus muscle.

Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26.

OBJECTIVE: To describe the time between treatment for choroidal melanoma and first diagnosis of metastatic disease, sites of metastasis, treatments for metastasis, and time between diagnosis of metastasis and death. DESIGN: Prospective, longitudinal follow-up of patients diagnosed with choroidal melanoma who were enrolled in 2 randomized trials conducted by the Collaborative Ocular Melanoma Study Group. METHODS: Systemic and laboratory evaluations were performed during follow-up according to a standard protocol for 2320 patients enrolled in the Collaborative Ocular Melanoma Study trials without evidence of melanoma metastasis or other primary cancer at baseline. RESULTS: Seven hundred thirty-nine patients were diagnosed with at least 1 site of metastasis during follow-up after treatment for choroidal melanoma. Five- and 10-year cumulative metastasis rates were 25% (95% confidence interval, 23%-27%) and 34% (95% confidence interval, 32%-37%), respectively. Liver was the most common site (89%). The death rate following the report of melanoma metastasis was 80% at 1 year (95% confidence interval, 77%-83%) and 92% at 2 years (95% confidence interval, 89%-94%). Overall survival after metastasis did not vary by baseline size of primary tumor nor treatment for metastasis (when known). Long-term survival after diagnosis of metastasis was uncommon; only 8 patients survived 5 or more years. CONCLUSION: Metastasis rate increased significantly with increasing primary tumor dimensions at time of patient enrollment. Prognosis after metastatic disease remains poor. Effective methods are needed to prevent, diagnose, and treat metastasis from choroidal melanoma.

Second primary cancers after enrollment in the COMS trials for treatment of choroidal melanoma: COMS Report No. 25.

OBJECTIVE: To report sites of second primary cancer and the time to first diagnosis during routine follow-up after treatment for choroidal melanoma. DESIGN: Prospective longitudinal follow-up of patients enrolled in 2 randomized trials conducted by the Collaborative Ocular Melanoma Study (COMS) Group. METHODS: Baseline and annual or semiannual systemic and laboratory evaluations were performed according to a standard protocol for 2320 patients enrolled in the COMS without evidence of melanoma metastasis or other primary cancer at baseline. Deaths were coded by a mortality coding committee. RESULTS: Subsequent to treatment for choroidal melanoma, a total of 222 patients were diagnosed with a second primary cancer other than basal or squamous cell skin cancer (5-year rate of 7.7% [95% confidence interval, 6.6%-9.0%]). The most common sites were prostate (23% of reported cases) and breast (17%); 12 of these 222 patients were diagnosed simultaneously with second primary cancers in 2 or more sites. Of these 222 patients, 113 died; 37 (33%) were coded as dead with melanoma metastasis, 33 (29%) as dead with a malignant tumor other than metastatic melanoma, and 13 (11%) as dead with a malignancy of uncertain origin. Radiotherapy did not significantly increase the development of second primary cancers. The rate of diagnosis of second primary cancer did not differ significantly by smoking status, although the rate in former smokers was increased vs that observed in either current smokers or those who never smoked. CONCLUSION: Routine medical surveillance for development of second primary cancers among patients treated for choroidal melanoma is important, especially for those with a history of smoking, regardless of the size of choroidal melanoma at the time of treatment.

Visual Acuity, Contrast Sensitivity and Color Vision Three Years After Iodine-125 Brachytherapy for Choroidal and Ciliary Body Melanoma.

PURPOSE: To report visual acuity, contrast sensitivity and color vision prior to, 1 year after, 2 years after and 3 years after iodine-125 brachytherapy for choroidal and ciliary body melanoma (CCM). DESIGN: Prospective interventional case series. PARTICIPANTS: Thirty-seven patients (37 eyes) with CCM. METHODS: Patients had best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, Pelli-Robson contrast sensitivity and Hardy-Rand-Rittler color vision measurement; comprehensive ophthalmology examination; optical coherence tomography; and ultrasonography at baseline prior to, 1 year after, 2 years after and 3 years after I-125 brachytherapy. MAIN OUTCOME MEASURES: Visual acuity, contrast sensitivity and color vision prior to, 1 year after, 2 years after and 3 years after brachytherapy. RESULTS: Nineteen (19) men and 18 women with mean age of 58 years (SD 13, range 30-78) prior to, 1 year after, 2 years after and 3 years after brachytherapy had mean best-corrected visual acuity of 77 letters (20/32), 65 letters (20/50), 56 letters (20/80) and 47 letters (20/125); contrast sensitivity of 30, 26, 22 and 19 letters; color vision of 26, 20, 17 and 14 test figures, respectively. Decrease in visual acuity, contrast sensitivity and color vision was statistically significant from baseline at 1 year, 2 years, and 3 years after brachytherapy. Decreased acuity at 3 years was associated with mid-choroid and macula melanoma location, ≥ 4.1 mm melanoma height, radiation maculopathy and radiation optic neuropathy. CONCLUSION: 1, 2 and 3 years after brachytherapy, eyes with CCM had significantly decreased visual acuity, contrast sensitivity and color vision.

Functional anatomy of the anophthalmic socket: insights from magnetic resonance imaging.

PURPOSE: Changes in anophthalmic socket anatomy can significantly compromise esthetics and motility after enucleation. This study evaluated such changes by using magnetic resonance imaging (MRI) of enucleated and fellow orbits. METHODS: High-resolution, surface coil MRI was performed in five patients after enucleation for uveal melanoma. Images were analyzed quantitatively to determine extraocular muscle (EOM) volume, maximum diameter, and length; orbital, optic nerve (ON), and orbital fat tissue (OFT) volume; and implant position. The fellow orbit was used as the control. Patients evaluated their satisfaction with the surgical results and were clinically examined. RESULTS: Rectus EOM volume was slightly but not significantly reduced on the surgical compared with the control side. Oblique EOM and OFT volumes were unchanged. Rectus EOM length was significantly reduced in the surgical side, but maximum EOM diameter in central gaze position was slightly but not significantly greater on the enucleated side. Rectus EOM paths were not qualitatively changed by enucleation and continued to exhibit the influence of the connective tissue pulleys, which retained motility, as appropriate to EOM contraction. Implants were located significantly posterior to the normal globe location. CONCLUSIONS: Enucleation does not significantly change EOM volume, but shortens EOM paths, a change that would be expected to alter their mechanical properties. EOM pulleys appear to retain their functional role in enucleated orbits.