Are Risk Factors for Growth of Choroidal Nevi Associated With Malignant Transformation? Assessment With a Validated Genomic Biomarker.

PURPOSE: To test the hypothesis that widely used clinical risk factors for growth of choroidal nevi are associated with malignant transformation. METHODS: Fine needle biopsy for assignment of gene expression profile (class 1 or class 2) was performed in 207 choroidal melanocytic tumors < 3.5 mm in thickness. The class 2 profile was employed as a validated biomarker for malignant transformation. The following data were collected: patient age and sex, tumor diameter and thickness, distance of posterior tumor margin from the optic disc, and the presence or absence of serous retinal detachment, orange lipofuscin pigment, drusen, retinal pigment epithelial fibrosis, retinal pigment epithelial atrophy, visual symptoms, and documented tumor growth. RESULTS: Clinical features associated with the class 2 profile included patient age > 60 years and tumor thickness > 2.25 mm (Fisher exact test, P = .002 for both). Documented growth was not associated with the class 2 profile (P = .5). The odds ratio of a tumor having the class 2 profile was 2.8 (95% confidence interval 1.3-5.9) for patient age > 60 years and 3.5 (95% confidence interval 1.4-8.8) for tumor thickness > 2.25 mm. For patients with both risk factors, the "number needed to treat" to identify 1 patient with a class 2 tumor was 4.3 (P = .0002). No other clinical feature or combination of features was associated with the class 2 profile. CONCLUSIONS: None of the widely used choroidal nevus risk factors for tumor growth, nor documented growth itself, is pathognomonic of malignant transformation as defined by class 2 gene expression profile. Patient age and tumor thickness may be helpful for identifying small choroidal melanocytic tumors that are more likely to have the class 2 profile. Observation for growth prior to treatment continues to be reasonable for most patients with suspicious choroidal nevi. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Noninvasive Electroretinography Assessment of Intravitreal Sustained-Release Methotrexate Microimplants in Rabbit Eyes.

PURPOSE: The purpose of this study is to noninvasively evaluate the safety and toxicity of a chitosan (CS) and polylactic acid (PLA)-based sustained-release methotrexate (MTX) intravitreal microimplant in normal rabbit eyes using electroretinography (ERG). METHODS: PLA-coated CS-based microimplants containing 400 µg of MTX and placebo microimplants (without drug) were surgically implanted in the vitreous of the right and the left eyes, respectively, in each of the 8 New Zealand rabbits using minimally invasive technique. At each predetermined time points (days 5, 12, 19, and 33), ERG was conducted on 2 rabbits to evaluate the safety of the microimplants administered in each eye. ERG was carried out using 2 protocols, scotopic and photopic, on each eye prior to surgery (PS) and prior to euthanasia (PE) conditions. The safety of the microimplants was assessed using statistical analysis of the ERG data (B/A ratio analysis, oscillatory potential analysis, and Naka-Rushton analysis) and subsequently quantifying and comparing functional integrity of the retina between the PS and PE conditions of each eye. RESULTS: Statistical analysis of the ERG data showed no change in retinal functional integrity because of the PLA-coated CS-based MTX microimplant and the placebo microimplant. ERG analysis also revealed absence of any evident bioelectrical dysfunction caused by the microimplants. CONCLUSION: ERGs were performed to determine whether the microimplants containing MTX and the placebo microimplants were associated with any profound retinal bioelectrical dysfunction that might be attributable to toxicity not apparent on histological studies of such eyes. The results shown in this report indicate that there were no such evident adverse effects of the microimplants or contained drug.

Ultrasonographical assessment of implanted biodegradable device for long-term slow release of methotrexate into the vitreous.

Our group has developed a biodegradable drug delivery device (micro-implant) for long-term slow intraocular release of methotrexate (MTX) that can be implanted in the peripheral vitreous. The purpose of this study was to assess the position of the implanted devices and the status of the adjacent vitreous and peripheral retina over time using B-scan ocular ultrasonography (US). In each of the eight New Zealand rabbits used in this study, a chitosan (CS) and poly-lactic acid (PLA)-based micro-implant containing approximately 400 µg of MTX and a placebo micro-implant without MTX were inserted into the peripheral vitreous of the right and left eyes, respective, employing minimally invasive surgery. B-scan US imaging was performed on all of the rabbits immediately after implant insertion and on two rabbits at each of several pre-determined time points post-insertion (post-insertion days 5, 12, 19, and 33) to evaluate the position of the micro-implants and identify any evident morphological changes in the micro-implants and in the peripheral retina and vitreous during treatment. US imaging revealed stable positioning of the PLA-coated CS-based MTX micro-implant and the placebo micro-implant in the respective eyes throughout the study and lack of any changes in size, shape or sonoreflectivity of the micro-implants or abnormalities of the peripheral vitreous or retina in any of the study eyes. In summary, US did not show any evident morphological changes in the micro-implants, shifts in post-insertion position of the micro-implants, or identifiable changes in the micro-implants or peripheral vitreous and retina of the study eyes.

Unnecessary clinical tests in ophthalmology.

PURPOSE: To define and discuss unnecessary clinical tests in ophthalmology, review the justifications commonly given by clinicians for obtaining unnecessary clinical tests, and suggest a more rational approach to clinical testing in the future. METHODS: The author defines an unnecessary clinical test as a test on a human subject that is unlikely to influence that patient's diagnosis, prognosis, or management or is performed exclusively, primarily, or in large part for research purposes. RESULTS: Examples of clinical tests the author categorizes as unnecessary are tests performed to evaluate a new or nonstandard diagnostic instrument or method; tests performed to evaluate sensitivity, specificity, and predictive value of a new instrument or method; tests obtained to provide images or data for future analysis, presentation, or publication; tests obtained routinely in patients of a certain class or category without regard to the individual's personal characteristics, recent clinical history, or clinical signs; and duplicate tests performed without retrieval and review of recent prior tests of the same types and determination of the quality of and findings revealed by those tests. Several justifications that are commonly given by clinicians for their ordering of unnecessary tests are presented, and each of these justifications is critiqued. The principal problems with unnecessary testing are increased costs of medical care, worsening rather than improvement in patient outcomes, and unethical practice. CONCLUSION: Unnecessary testing is perhaps an unavoidable aspect of current clinical ophthalmic practice in the United States. In spite of this, clinicians (especially academic ophthalmologists) need to be aware of this issue and take appropriate steps to minimize such testing.