George E. Sanborn

The effect of the aldose reductase inhibitor, ponalrestat, on the progression of diabetic retinopathy

The objective of this study was to evaluate the effects of ponalrestat, an aldose reductase inhibitor, on the progression of diabetic retinopathy. In this study, 62 patients with diabetes mellitus underwent a double-masked placebo-controlled clinical trial comparing the effect of ponalrestat 600 mg per day with a placebo on the progression of diabetic retinopathy. Both groups were comparable in terms of age, gender distribution, diabetes duration, metabolic control, and presence and severity of diabetic retinopathy. Seven-field stereo fundus photographs were performed at 0 (baseline), 12, and 18 months; 49 patients completed the study (26 in the ponalrestat group and 23 in the placebo group). In both treatment groups, a significant progression of diabetic retinopathy as evaluated by the Early Treatment Diabetic Retinopathy Study classification was observed (Wilcoxon Rank-Sum Test, p less than 0.05). No difference was observed in the progression of retinopathy between the two treatment groups (p = 0.96). The number of microaneurysms increased in the two study groups (from 5.6 +/- 1.2 to 10.5 +/- 1.3 in the placebo group and from 10.3 +/- 1.4 to 12.7 +/- 1.4 in the ponalrestat group); however, the increase was statistically significant only in the placebo group (p less than 0.05). When the increase in the number of microaneurysms was evaluated by change of category of microaneurysm count, no significant difference was observed. We conclude that ponalrestat at a dose of 600 mg per day has no clinically significant effect on the progression of diabetic retinopathy.

Prevention of metastasis of intraocular melanoma in mice treated with difluoromethylornithine

The antimetastatic potential of a novel chemotherapeutic agent, alpha-difluoromethylornithine (DFMO), was evaluated in a murine model of intraocular melanoma. In vivo studies demonstrated that DFMO retarded the growth and spontaneous metastasis of murine intraocular melanomas. Further studies indicated that oral DFMO also exercised antimetastatic effects against the blood-borne stage of melanoma metastases. In vitro studies revealed that DFMO exerted impressive antiproliferative effects on three murine melanoma cell lines, four human cutaneous melanoma cell lines, one human uveal melanoma cell line, and one conjunctival melanoma cell line. DFMO inhibited in vitro DNA synthesis in human cutaneous melanoma cell lines by 84%–98% and that in two human ocular melanoma cell cultures by 62% and 86%, respectively. DFMO possesses several characteristics that render it an attractive chemotherapeutic agent for potential use in the management of uveal melanoma. These include its antiproliferative effect against a wide range of murine and human melanomas, its extremely low toxicity, and its ease of administration.

Efficacy of Dacarbazine (DTIC) in preventing metastases arising from intraocular melanomas in mice

At present there are no chemotherapeutic agents that have been proven to be effective in either preventing or retarding the progression of metastases arising from uveal melanomas in human subjects. Dacarbazine (DTIC), the single most effective chemotherapeutic agent in the treatment of cutaneous melanoma, is a potentially useful therapeutic modality for use as an antimetastatic agent in uveal melanoma. However, DTIC has not been evaluated for its ability to impede metastases originating from intraocular melanomas. The present study assessed the antimetastatic efficacy of DTIC in a murine intraocular melanoma model. The results indicate that treatment with DTIC resulted in sharp reductions in the number of spontaneous metastases and a significant prolongation of survival time. Dose-response studies indicated that exceedingly high doses of DTIC were necessary to produce antimetastatic effects even when drug treatment was combined with the calcium channel blocker verapamil. Collectively, the results indicate that DTIC can be an effective adjunctive therapeutic agent when administered at the time of enucleation of the melanoma-containing eye but is ineffectual if administered subsequent to surgery.

Rheumatoid Nodules of the Upper Lid: Report of a Case

Severe rheumatoid arthritis with rheumatoid nodules on the left upper lid occurred in a 72-year-old woman. Rheumatoid nodules may break down either spontaneously or secondary to trauma. When breakdown occurs, debridement and closure are recommeneded.

Contrast sensitivity versus static visual field testing during experimental elevation of intraocular pressure.

Contrast sensitivity testing has been recommended as a more sensitive indicator of early visual loss than visual field testing. Using gravity inversion to induce an intraocular pressure rise, we performed contrast sensitivity testing on each eye of 10 normal subjects in the upright and inverted positions. Contrast sensitivity results were not altered in the head-down position, even though in 5 of the 10 subjects (7 of 20 eyes), visual field alterations on static perimetry were elicited during inversion. In both of these evaluations, the subjects results in the upright position served as the control, freeing us from reliance upon age-matched populations. We conclude that precise measurement of static thresholds with automated perimetry is more sensitive than routine contrast sensitivity testing in detecting visual dysfunction related to transient acute elevations of intraocular pressure.

Evaluation of a combination digital retinal camera with spectral-domain optical coherence tomography (SD-OCT) that might be used for the screening of diabetic retinopathy with telemedicine: A pilot study

AIMS Pilot study to determine whether an instrument combining a non-mydriatic retinal camera and spectral domain optical coherence tomography (SD-OCT) is effective for screening patients with diabetic retinopathy (DR). METHODS Case series conducted between 2012 and 2013. DR imaged with a retinal camera/SD-OCT instrument viewed remotely was compared to a dilated examination by a retina specialist. RESULTS The combination instrument was better than the retina specialist in detecting more severe retinopathy, primarily because of the SD-OCT. For severe retinopathy (grade ≥ 3), the image grader had better sensitivity (87.3% [95% CI: 75.5%, 94.7%]) than the retina examiner (76.4% [95% CI: 63.0%, 86.8%]). Specificities were similar between the instrument grader (96.0% [95% CI: 86.3%, 99.5%]) and retina examiner (100.0% [95% CI: 92.9%, 100.0%]). When identifying diabetic macular edema (ME), the retina examiner only identified 47.6% (20/42) of eyes with ME detected by SD-OCT. The instrument was better than a dilated retinal examination in detecting ME and not as good at detecting mild or proliferative retinopathy. CONCLUSIONS As used in this study, the instrument was more effective in identifying DR than was the current recommendation of a dilated and comprehensive eye examination. SD-OCT is needed to accurately identify DR in a screening setting.

Isolated symptomatic peripheral neuropathy in type 1 insulin-dependent diabetes mellitus

Diabetic neuropathy is probably the most frequent of the chronic complications of diabetes, and is usually found in association with diabetic retinopathy and/or nephropathy. We report seven patients with long-standing insulin-dependent diabetes mellitus in whom symptomatic peripheral neuropathy was the first and only documented complication. The diagnosis of peripheral symmetrical neuropathy was based on the presence of symptoms and abnormal physical findings, confirmed with abnormal electrophysiological and/or vibratory and thermal threshold measurements. Diabetic retinopathy and nephropathy were absent. We conclude that in some type 1 insulin-dependent diabetic patients, similar to what has been reported in type 2 non-insulin-dependent diabetes, peripheral neuropathy may be the first chronic complication to become manifest. This observation provides additional evidence to suggest that each of the diabetic complications may have a different pathogenic mechanism.