Optical Coherence Tomography Imaging of the Palisades of Vogt to Assist Clinical Evaluation and Surgical Planning in a Case of Limbal Stem-Cell Deficiency

PURPOSE: To describe the use of volumetric optical coherence tomography (OCT) imaging to assist evaluation of a patient referred for autologous limbal stem cell transplant. METHODS: This is a case report of a fifty year-old patient presenting with unilateral limbal stem cell deficiency who was referred for autologous limbal stem cell transplant. The presence of Salzmann's nodules in the donor eye raised questions about the efficacy of transplantation, prompting examination of both eyes using volumetric OCT imaging to determine whether there were palisades of Vogt (POV) present. Image volumes were acquired in all clock hours and were compared against those of an age-matched normal subject. RESULTS: Palisades were found in both eyes, although in both eyes there were fewer palisade ridges, and those that were present were not as distinct as those of the normal subject. The OCT volumes also showed that stromal scarring was present only in the anterior stroma of the intended transplant eye. These findings suggested that the patient may be able to sustain a deep anterior lamellar keratoplasty (DALK) without an autologous transplant, which would spare any insult to the opposing eye and require less surgery to restore vision in the affected eye. Nine months post-surgical follow up revealed significant improvement in visual acuity and no scar tissue development. CONCLUSION: OCT evaluation of the POV provides detailed information to the clinician that may assist in diagnosis and evaluation of patients prior to transplantation. Further development of this technique is necessary to make it clinically available

Ulcerative keratitis in gatrointestinal stromal tumor patients treated with perifosine

19664 Background: Perifosine is a novel, oral, alkylphospholipid with antiproliferative properties attributed to Akt inhibition. We describe the ocular findings in 5 patients enrolled in phase I/phase II trials of perifosine in combination with imatinib for treatment of advanced GIST. Methods: The medical records of 5 patients who developed peripheral ulcerative keratitis while receiving perifosine and imatinib were retrospectively reviewed. Results: 1 man and 4 women ranged in age from 43 to 72 (median, 57 years). The ocular symptoms included redness, irritation, tearing, photophobia and a gradual decrease in vision. Slit lamp biomicroscopy in each case revealed a peripheral, paralimbal, ring-shaped, superficial stromal infiltration and ulcerative keratitis (UK), reminiscent of the autoimmune keratitis in conditions such as rheumatoid arthritis. The best corrected visual acuity in the affected eye(s) ranged from 20/25 to 20/300 (median 20/70). The UK was unilateral in 3 and bilateral in 2 patients; it was NCI grade II in all. All 6 patients had imatinib-resistant metastatic GIST and had continued on the highest dose of imatinib tolerated and initiated therapy with perifosine 100 mg daily or 900 mg weekly. Time from start of perifosine therapy to diagnosis of UK ranged from 1 to 3 months (median, 2). A combination of topical steroids, topical antibiotics and lubricating drops were used to manage UK. In the first 3 patients, UK was initially treated with topical antibiotics without improvement, but subsequently improved significantly once topical steroids were added. In 5 of 6 patients, the visual acuity improved with this regimen. Conclusions: UK may occur as a side effect of perifosine and shares features of autoimmune forms of keratitis. It is possible that imatinib in combination with perifosine is contributing to this toxicity. Topical steroids improve the signs and symptoms of UK and early treatment with topical steroids may lessen the potential risk of permanent corneal scarring and visual loss. The visual loss associated with perifosine can be reversible with close monitoring and judicious use of topical steroids, topical antibiotic coverage, and lubrication. No significant financial relationships to disclose. </jats:p

Topical Recombinant Human Nerve Growth Factor (Cenegermin) for Neurotrophic Keratopathy: A Multicenter Randomized Vehicle-Controlled Pivotal Trial.

PURPOSE:To evaluate the efficacy and safety of topical cenegermin (recombinant human nerve growth factor) in patients with neurotrophic keratopathy. DESIGN:Multicenter, randomized, double-masked, vehicle-controlled trial. PARTICIPANTS:Patients with neurotrophic persistent epithelial defect with or without stromal thinning. METHODS:The NGF0214 trial, conducted among 11 sites in the United States, randomized 48 patients 1:1 to cenegermin 20 μg/ml or vehicle eye drops, 6 drops daily for 8 weeks of masked treatment. Follow-up was 24 weeks. Safety was assessed in all patients who received study drug. Efficacy was assessed by intention to treat. MAIN OUTCOME MEASURES:The primary end point was healing of the neurotrophic lesion (persistent epithelial defect or corneal ulcer) after 8 weeks of masked treatment. Masked central readers measured neurotrophic lesions in randomized clinical pictures, then assessed healing status conventionally (&lt;0.5 mm of fluorescein staining in the greatest dimension of the lesion area) and conservatively (0-mm lesion staining and no other residual staining). Secondary variables included corneal healing at 4 weeks of masked treatment (key secondary end point), overall changes in lesion size, rates of disease progression, and changes in visual acuity and corneal sensitivity from baseline to week 8. RESULTS:Conventional assessment of corneal healing showed statistically significant differences at week 8: compared to 7 of 24 vehicle-treated patients (29.2%), 16 of 23 cenegermin-treated patients (69.6%) achieved less than 0.5 mm of lesion staining (+40.4%; 95% confidence interval [CI], 14.2%-66.6%; P = 0.006). Conservative assessment of corneal healing also reached statistical significance at week 8: compared to 4 of 24 vehicle-treated patients (16.7%), 15 of 23 cenegermin-treated patients (65.2%) achieved 0 mm of lesion staining and no other residual staining (+48.6%; 95% CI, 24.0%-73.1%; P &lt; 0.001). Moreover, the conservative measure of corneal healing showed statistical significance at week 4 (key secondary end point). Compared to vehicle, cenegermin-treated patients showed statistically significant reductions in lesion size and disease progression rates during masked treatment. Cenegermin was well tolerated; adverse effects were mostly local, mild, and transient. CONCLUSIONS:Cenegermin treatment showed higher rates of corneal healing than vehicle in neurotrophic keratopathy associated with nonhealing corneal defects