Radial optic neurotomy using nasal and temporal approach incisions: histopathologic study in human cadaver eyes.

OBJECTIVE: To examine the structural effect of radial optic neurotomy (RON) using nasal and temporal approach incisions on the nasal side of the optic nerve (ON) using dominant and nondominant hands in human cadaver eyes. METHODS: Transvitreal RON was performed in 9 eyes with a microvitreoretinal blade by a right-handed surgeon. A nasal approach was used in 4 left eyes (using the right hand) and in 2 right eyes (using the left hand), and a temporal approach was used in 3 right eyes (using the right hand). Histologic sections were examined for depth of nerve penetration and for effect on critical structures. RESULTS: The scleral canal was fully incised in all cases. The mean depth of nerve penetration was 555 micro25 microing the nasal approach and 246.7 microing the temporal approach) (P =.12). The globe was not ruptured in any eye. In a single right eye approached temporally using the right hand, the adventitial sheath of the central retinal artery was lacerated. CONCLUSIONS: RON in human cadaver eyes results in lysis of the scleral canal at the ON head. Greater depth and improved safety of incision can be achieved by always approaching the incision from the nasal side of the ON using the dominant or nondominant hand.

A study of iridectomy histopathologic features of latanoprost- and non-latanoprost-treated patients.

OBJECTIVES: To examine the histopathologic features of iridectomy specimens from patients undergoing glaucoma surgery and to compare histologic abnormalities in a group of patients with a history of latanoprost therapy with those in a group of patients who had no history of prostaglandin therapy (controls). METHODS: Iridectomy specimens and patient history forms were submitted to the central Latanoprost Pathology Center. These were independently examined by 3 ophthalmic pathologists in a masked fashion. Specimens were evaluated for malignant, premalignant, and other changes including differences in levels of pigmentation, degrees of cellularity, inflammation, vascular abnormalities, and changes in the iris pigment epithelium. RESULTS: Specimens were received from 449 patients with a history of latanoprost treatment and 142 patients who had no history of treatment with latanoprost or other prostaglandin analogues. No evidence of malignant or premalignant changes was found. In latanoprost-treated irides, the prevalence of iris freckles was higher (P = .001) than in control irides, as was the combined number of stromal fibroblasts and melanocytes (P<.001). In a subgroup of specimens received through June 2002, there was no significant difference in mean melanocyte counts (P=.35) obtained by immunohistochemical staining techniques between the latanoprost-treated and control groups. CONCLUSIONS: These findings support previous studies indicating that latanoprost-induced eye color changes are due to an increased amount of melanin within the iris stromal melanocytes. The increased numbers of freckles may be a focal manifestation of this effect.

Slitlamp, specular, and light microscopic findings of human donor corneas after laser-assisted in situ keratomileusis.

OBJECTIVE: To examine slitlamp, specular, and light microscopic features of human donor corneas known to have undergone laser-assisted in situ keratomileusis (LASIK). METHODS: Twenty-six donor corneas known to have undergone LASIK prospectively underwent slitlamp examination with particular attention to the presence of a flap edge, as well as specular microscopy with particular attention to the presence of highly reflective particles in the stroma corresponding to the LASIK interface. Central endothelial cell density and pachymetery were obtained. They were compared with 26 control donor corneas without LASIK. Eleven LASIK donor corneas were processed for histology. Twenty-six donor corneas with no known prior keratorefractive surgery also underwent similar slitlamp examination and specular microscopy to serve as controls. RESULTS: Twelve (46%) of 26 LASIK donor corneas had an obvious flap edge, and 10 (39%) had a subtle flap edge by slitlamp examination. Four (15%) had infiltrates by slitlamp examination, of which 3 were confirmed by histopathologic examination. Highly reflective particles were seen by specular microscopy in the stroma of 23 (88%) of 26 LASIK donor corneas, but only 1 (4%) of 26 control donor corneas had a single highly reflective particle in the stroma (P<.001). The mean central endothelial cell counts were similar: 2138 cells/mm(2) in the LASIK group compared with 2250 cells/mm(2) in the controls (P =.39). Vacuolization and pyknosis of keratocytes was a consistent histopathologic finding after LASIK. Metallic particles at the interface were not detected by histology. CONCLUSIONS: Detection of a flap edge by slitlamp examination may detect at least half of the donor corneas that may have undergone LASIK. The detection of highly reflective stromal particles may form an effective basis for screening for LASIK donor corneas using specular microscopy and requires further study.

Toxicity and dose-response studies of 1-alpha hydroxyvitamin D2 in LH-beta-tag transgenic mice.

PURPOSE: To determine the effectiveness of a vitamin D analog, 1alpha-hydroxyvitamin D(2) (1alpha-OH-D(2)), in inhibiting retinoblastoma in a transgenic retinoblastoma model (LHbeta-Tag mouse) and to evaluate its toxicity. DESIGN: Experimental study using an animal (LHbeta-Tag transgenic mouse) randomized (controlled) trial. PARTICIPANTS AND CONTROLS: Two hundred seventeen LHbeta-Tag transgene-positive 8- to 10-week-old mice total; 179 drug-treated animals, 38 control animals. METHODS: Mice were fed a vitamin D- and calcium-restricted diet and were randomized to treatment groups receiving control (vehicle), or 0.1, 0.3, 0.5, or 1.0 micro g/day of 1alpha-OH-D(2) via oral gavage 5 times weekly for 5 weeks. Body weight was measured at the start of treatment and twice weekly during treatment. Animals were euthanized on the last day of treatment. The eyes were enucleated, processed histologically, and serially sectioned. Representative sections from the superior, middle, and inferior regions of each globe were examined microscopically and tumor areas were measured using Optimas software. Serum was collected for serum calcium levels. Kidneys were removed for histologic processing and were analyzed microscopically for kidney calcification. MAIN OUTCOME MEASURES: Mean tumor area was measured to determine drug effectiveness. Toxicity was assessed by survival, weight loss over the treatment period, serum calcium, and kidney calcification. RESULTS: The mean tumor size in each 1alpha-OH-D(2) group was smaller than controls (all P values < 0.02): control, 90,248 micro m(2); 0.1 micro g, 31,545 micro m(2); 0.3 micro g, 16,750 micro m(2); 0.5 micro g, 30,245 micro m(2); and 1.0 micro g, 16,049 micro m(2). No dose-dependent response curve was evident. The survival percentage for each group was as follows: control, 97%; 0.1 micro g, 91%; 0.3 micro g, 88%; 0.5 micro g, 70%; and 1.0 micro g, 63%. Mortality was higher in the 0.5- micro g and 1.0- micro g doses (P values < 0.01) compared with other treatment groups and with the control group. Serum calcium levels were significant in all treatment groups compared with controls (all P values < 0.0001). CONCLUSIONS: In the LHbeta-Tag mouse, 1alpha-OH-D(2) inhibits retinoblastoma with no significant increase in mortality in lower doses (0.1-0.3 micro g). 1alpha-OH-D(2) has approval by the Food and Drug Administration as an investigative drug for cancer treatment, and has shown efficacy with low toxicity in adult cancer trials. 1alpha-OH-D(2) meets the criteria for human clinical trials.

Iris melanocyte numbers in Asian, African American, and Caucasian irides.

PURPOSE: The anatomical basis for iris color has long been a controversial issue in ophthalmology. Recent studies demonstrated that in Caucasians, blue-eyed, gray-eyed, and hazel-eyed individuals have comparable numbers of iris melanocytes. The present investigation was carried out to compare melanocyte numbers in the irides of Asian, African American, and Caucasian brown-eyed individuals. METHODS: Paraffin-embedded sections from 71 brown-colored irides were incubated with rabbit anti-cow antibody against S100a, linked with an FITC conjugate antibody, and counterstained with Evans blue. Cells were counted under a fluorescence microscope and scored as melanocytes or other cells. Cell number, density, and iris area were calculated for each specimen. RESULTS: Caucasian and African American irides had comparable mean total melanocyte numbers. Asian irides had fewer total melanocytes than African American (P = .042) and Caucasian (P = .001) irides and smaller total number of cells (ie, melanocytes plus other cells) than African American (P = .054) or Caucasian (P = .009) irides. CONCLUSIONS: There is a statistically significant smaller mean total melanocyte number and mean total cellularity in Asian irides as compared to Caucasian and African American irides. This difference appears to be due to the combination of smaller iris area and lower melanocyte density in the Asian irides. The possibility exists that this may be a factor in ethnic variations in certain ocular diseases.

Toxicity and dose-response studies of 1 alpha-hydroxyvitamin D2 in LH beta-Tag transgenic mice.

PURPOSE: The study objective is to determine the effectiveness of a vitamin D analogue, 1 alpha-hydroxyvitamin D2 (1 alpha-OH-D2), in inhibiting retinoblastoma in a transgenic retinoblastoma model (LH beta-Tag mouse) and to evaluate its toxicity. Previous studies of 1 alpha-OH-D2 in athymic mice with human retinoblastoma xenografts suggested efficacy in tumor suppression and suitability for human treatment. METHODS: LH beta-Tag mice (N = 142), 8 to 10 weeks old, were randomly assigned to treatment groups receiving either control (vehicle) or 0.1, 0.3, 0.5, or 1.0 microgram/day of 1 alpha-OH-D2 via oral gavage five times a week for 5 weeks. Animals were then euthanized. The eyes were enucleated, processed histologically, and serially sectioned. Three sections of each eye were microscopically examined, and mean tumor area was measured using Optimus software. Toxicity was assessed by mortality, weight loss, serum calcium levels, and kidney calcification. RESULTS: The mean tumor size in each 1 alpha-OH-D2 group was smaller than in controls (P values < .02): control, 90,248 microns 2; 0.1 microgram, 31,545 microns 2; 0.3 microgram, 16,750 microns 2; 0.5 microgram, 30,245 microns 2; and 1.0 microgram, 16,049 microns 2. No dose-dependent response curve was evident. Mortality was higher in the groups receiving the 0.5 microgram and 1.0 microgram doses (P values < .01) than in the other treatment groups and the control group. CONCLUSION: In the LH beta-Tag mouse, 1 alpha-OH-D2 inhibits retinoblastoma with no increased mortality at lower doses (0.1 to 0.3 microgram). 1 alpha-OH-D2 has been approved by the Food and Drug Administration as an investigative drug for cancer treatment and has shown efficacy with low levels of toxicity in adult cancer trials. 1 alpha-OH-D2 meets the criteria for human clinical trials.

Xeroderma pigmentoso y carcinoma intraocular / Pigmentoso Xeroderma and intraocular carcinoma

Objetivo: Mostrar las manifestaciones oculares en un paciente con xeroderma pigmentoso. Material. Estudio clínico, patológico, inmunohistoquimica de una paciente con xeroderma pigmentoso con manifestaciones oculocutáneas. Resultados: Los resultados mostraron la presencia un carcinoma escamoso corneo conjuntival con invasión de la cámara anterior y uvea anterior. Conclusiones: El xeroderma pigmentoso es una enfermedad genética que puede generar enfermedades graves a nivel ocular como son los tumores malignos.