Anna S. Kitzmann

The Incidence of Central Serous Chorioretinopathy in Olmsted County, Minnesota, 1980–2002

PURPOSE To determine the incidence of central serous chorioretinopathy (CSC) in Olmsted County, Minnesota from 1980 to 2002, determine the associated risk factors for CSC based on previously reported risk factors, investigate for any new risk factors not previously reported, and determine a population-based recurrence rate. DESIGN Population-based retrospective cohort and case-control study. PARTICIPANTS Cases were all patients with newly diagnosed CSC in Olmsted County Minnesota, from January 1, 1980 through December 31, 2002. Controls were selected from the same general population. Control group 1 patients were matched for age, gender, length of medical follow-up, and index date (corresponding with date of diagnosis for cases). Control group 2 patients were matched for all the same criteria as control group 1, and they had documented normal eye examination results. METHODS Using the Rochester Epidemiology Project medical records linkage system, which captures virtually all medical care provided to residents of Olmsted County, Minnesota, we identified all cases of CSC in county residents between 1980 and 2002. We reviewed the entire medical record of cases and applied standardized criteria for CSC. The medical records of cases and controls were reviewed for the presence of risk factors as well. MAIN OUTCOME MEASURE Incidence of CSC. Secondary outcomes were also evaluated. RESULTS There were 74 cases (63 men, 11 women) of CSC. Mean annual age-adjusted incidences per 100 000 were 9.9 (95% confidence interval [CI], 7.4-12.4) for men and 1.7 (95% CI, 0.7-2.7) for women. The incidence of CSC was approximately 6 times higher in men than in women (P<0.001). There were no significant risk factors identified for CSC. Twenty-three (31%) of the 74 patients with CSC had recurrences. The mean number of recurrences was 1.5 (range, 1-4). Median time from diagnosis to recurrence was 1.3 years (range, 0.4-18.2). CONCLUSION The incidence of CSC has not previously been reported in a population-based study. In accordance with previous studies, we found that CSC occurs more frequently in men than in women.

INTRAOCULAR USE OF RITUXIMAB

PurposeTo evaluate the toxicity of 1 mg of intraocular rituximab and to present a small case-series of patients treated with intravitreal rituximab.MethodsRituximab (1 mg/0.1 ml) was injected in the vitreous of one eye of three Dutch-belted rabbits. Two animals were injected with balanced salt solution as controls. At 1 month the rabbits were killed and the eyes examined by light microscopy. Three patients (five eyes) with intraocular lymphoma were also treated with a 1 mg injection of rituximab.ResultsThe treated rabbit eyes and the control eyes showed no light microscopic evidence of ocular toxicity at 1 month following injection. The five human eyes of three patients have shown no evidence of intraocular toxicity with a median follow-up time of 3.6 months (range 2.0–6.4 months). One patient received a total of four injections in the right eye and three injections in the left eye.ConclusionIntravitreal rituximab at a dose of 1 mg does not appear to cause toxicity in rabbit eyes and in the five eyes of three patients.

Comparison of corneal endothelial cell images from a noncontact specular microscope and a scanning confocal microscope

Purpose: We compared endothelial cell density (ECD) from images recorded by the ConfoScan 3 confocal microscope and a noncontact specular microscope. Methods: Endothelial micrographs of 50 normal corneas of 25 subjects were acquired by a Konan Noncon Robo noncontact specular microscope (Konan Medical, Inc., Hyogo, Japan) and a ConfoScan 3 confocal microscope (Nidek Technologies, Inc, Greensboro, NC). ECD was determined in images from both instruments by using the HAI CAS System Corners Method (HAI Labs, Inc., Lexington, MA). Distances in the images from both machines were calibrated from images of an external scale. Images from the ConfoScan 3 were also assessed using the automated endothelial analysis software provided by the manufacturer, with and without manual correction. Results: The ECD was 2634 ± 186 cells/mm2 (mean ± SD) and 2664 ± 173 cells/mm2 by the Robo and ConfoScan 3 Corners methods, respectively. Differences between these 2 methods were not significant. When the automated analysis software was used, however, significant differences were found (P = 0.001). The uncorrected analysis program provided with the ConfoScan 3 indicated a higher ECD (2742 ± 284 cells/mm3) than the Corners method did with images from the Robo and ConfoScan 3. The ECD from the manually corrected ConfoScan 3 method was 2716 ± 229 cells/mm3, not significantly different from the ConfoScan 3 Corners method but significantly different from the Robo Corners method. Conclusions: The ConfoScan 3 can be used interchangeably with the Robo when the Corners method is used to assess ECD and the magnification of both microscopes is calibrated with an external scale. If the proprietary software provided with the ConfoScan 3 is used, it should be manually corrected.

Clinicopathologic correlations in 646 consecutive surgical eye specimens, 1990-2000

All surgical eye specimens examined in our pathology laboratory between January 1, 1990, and July 31, 2000 (N = 646), were classified by surgical procedure (enucleation, evisceration, or exenteration) and pathologic diagnosis. Among 523 enucleated globes (81.0%), 252 (48.2%) contained tumors, of which 208 were intraocular malignant melanomas. Nonneoplastic causes for enucleation included glaucoma (67/523 [12.8%]), phthisis bulbi (61/523 [11.7%]), and recent trauma (59/523 [11.3%]). Sixty-seven specimens (10.4%) had been eviscerated. Fifty-six specimens (8.7%) were obtained by exenteration performed to manage malignant tumors originating in or invading the orbit. Between 1990 and 2000, the percentage of procedures performed to remove neoplasms decreased from 65% to 38%, procedures performed to treat glaucoma increased from 4% to 29%, and those to treat phthisis bulbi increased from 8% to 13%. The numbers of procedures remained relatively constant for trauma and for infectious and inflammatory diseases.

Incidence and severity of neovascularization in oxygen- and metabolic acidosis-induced retinopathy depend on rat source

Purpose. We have previously described oxygen-induced retinopathy (OIR) and metabolic acidosis-induced retinopathy (MAIR) in the neonatal rat, both of which are analogous to human retinopathy of prematurity (ROP). Given that rats of identical strain from two commercial suppliers are phenotypically different, we investigated the incidence and severity of preretinal neovascularization (NV) in rats from different suppliers using the OIR and MAIR models. Methods. Using our established models for OIR and MAIR, 400 newborn Sprague-Dawley rats, obtained from Harlan Laboratories (HSD) and Charles River Laboratories (CRSD), were raised in 16 expanded litters of 25 (6 OIR and 10 MAIR). Beginning at day 1 of life, OIR litters (3 HSD, 3 CRSD) were exposed to 7 daily cycles of hyperoxia (80% O 2, 20.5 hours) and hypoxia (10% O 2, 0.5 hours) with a gradual return to 80% O 2 over 3 hours. OIR rats were sacrificed after 5 days of room air recovery. MAIR litters (5 HSD, 5 CRSD) were raised in room air and gavaged twice daily with NH 4 Cl (10 mM/kg body weight) from day 2 through day 4. MAIR rats were sacrificed after 3 days of recovery. For both OIR and MAIR litters, retinae from left eyes were dissected, ADPase-stained, and flatmounted. Presence and severity of NV was scored and retinal vascular areas measured by a masked observer. Results. In OIR rats, the incidence of NV was higher in CRSD rats than HSD rats (73% vs. 45%, p= 0.002). NV was more severe in CRSD rats than HSD rats (median clock hours 2 vs. 0, p= 0.0001). In MAIR rats, the incidence of NV was comparable between CRSD and HSD rats (29% vs. 34%, p = 0.53) and there was no significant difference in the severity of NV. Conclusions. Sprague-Dawley rats obtained from two independent commercial sources differed in their incidence and severity of NV associated with OIR, but not with MAIR. Future genetic studies are warranted to investigate the differences between CRSD and HSD rats, which might yield further clues into the pathogenesis of ROP.

Histologic Findings in T-cell Lymphoma Infiltration of the Optic Nerve

OBJECTIVE To report the clinical and histologic features of lymphomatous infiltration of the optic nerve by systemic T-cell non-Hodgkins lymphoma (NHL). DESIGN Interventional case report. PARTICIPANT A patient with peripheral T-cell NHL. METHODS A 39-year-old man with a diagnosis of peripheral T-cell NHL, stage IV, with CNS involvement and decreased vision was found to have lymphomatous infiltration of the optic nerves. MAIN OUTCOME MEASURE Visual acuity. RESULTS Despite treatment with chemotherapy and an optic nerve sheath fenestration, the patient lost vision in the right eye and subsequently underwent an optic nerve biopsy. The histopathology showed diffuse infiltration with a clonal population of lymphocytic cells that were CD3 positive and CD20 negative, consistent with T-cell NHL. CONCLUSION Optic nerve infiltration from systemic B-cell lymphoma is rare and has been reported; we report an unusual case of bilateral optic nerve infiltration secondary to peripheral T-cell NHL.

Histologic studies of the intraocular toxicity of imatinib mesylate in rabbits

PurposeTo evaluate histologic signs of toxicity of the protein tyrosine kinase inhibitor, imatinib mesylate, in rabbit eyes.MethodsTwenty Dutch-belted rabbits underwent intravitreal injections of 0.1 ml solutions of imatinib mesylate. Ten rabbits were killed and enucleated 1 week after injection of imatinib mesylate (1.65 mg (four eyes), 165 μg (four eyes), and 16.5 μg (two eyes)). Ten rabbits injected with imatinib mesylate (165 μg (five eyes) and 825 μg (five eyes)) were enucleated 1 month later. Eyes were fixed in 10% formalin and stained with haematoxylin and eosin for microscopic examination.ResultsAll four eyes injected with 1.65 mg of imatinib mesylate and enucleated at 1 week demonstrated ocular toxicity. All four eyes injected with 165 μg and enucleated at 1 week showed no ocular toxicity. One of the two eyes injected with 16.5 μg and enucleated at 1 week revealed focal areas of subretinal fluid and retinal undulations, suggestive of retinal oedema. None of the 10 eyes injected with imatinib mesylate at either the 165 or 825 μg dose and enucleated at 1 month showed ocular toxicity.ConclusionsImatinib mesylate at 1.65 mg caused extensive retinal toxicity in rabbit eyes. In contrast, lower doses did not appear to cause toxicity, but may be associated with retinal oedema.

A Splice-Site Mutation in CCM1/KRIT1 is Associated with Retinal and Cerebral Cavernous Hemangioma

Purpose: To report a case of a unilateral retinal cavernous hemangioma associated with a novel splice-site mutation in CCM1/KRIT1. Methods: An 11-year-old girl was noted to have an asymptomatic retinal cavernous hemangioma in the left eye. CCM1/KRIT1 was screened for mutations. Results: Genetic evaluation of CCM1/KRIT1 revealed a single guanine-to-cytosine transversion in the invariant splice acceptor consensus sequence of intron 8 (c.1146-1G→C), which is predicted to result in abnormal protein splicing. Conclusions: Mutations in CCM1/KRIT1 may be found in asymptomatic patients with retinal cavernous hemangioma.

Progressive increase in the angle of deviation in acquired nonaccommodative esotropia of childhood.

PURPOSE Although the angle of deviation in patients with congenital esotropia has been shown to increase during the early preoperative period, few data exist regarding this change in other forms of childhood esotropia. The primary objective of this study was to investigate whether the angle of deviation increases with time in patients with acquired nonaccommodative esotropia (ANAET). METHODS The medical records of all children whose ANAET was diagnosed at East Tennessee State University College of Medicine from August 1, 1995, through October 1, 2001, were retrospectively reviewed. All patients were assessed for any change in the amount of their strabismic angle and associated risk factors. RESULTS Eighty-two patients with ANAET were identified, and all except 3 underwent more than one examination. Of the 79 children who underwent more than one examination, 26 (32.9%) displayed an angle increase of > or =10 prism diopters (PD) during a median follow-up period of 2.9 months. The ANAET of those patients whose angle increased by > or =10 PD was diagnosed (28.4 months of age vs 45.5 months of age, P =.003), and they underwent surgery (35.9 months of age vs 53.3 months of age, P =.003) at a significantly younger median age than those whose angle increased <10 PD. CONCLUSIONS The angle of deviation of approximately one third of patients with ANAET in this study increased at least 10 PD in the early preoperative period. This increase occurs more often in younger patients and underscores the importance of performing serial measurements of the deviating angle before surgical intervention is undertaken.

Short-term motor and sensory outcomes in acquired nonaccommodative esotropia of childhood.

Information on the management of acquired nonaccommodative esotropia (ANAET) of childhood is incomplete. Most prior reports combine the results of patients with both accommodative and nonaccommodative esodeviations. The primary objective of this study was to describe the early postoperative motor and sensory results of children with acquired nonaccommodative esotropia. The medical records of 72 consecutive children with ANAET who underwent surgical correction at East Tennessee State University College of Medicine from August 1, 1995 through October 1, 2001 were retrospectively reviewed. The median age at surgery for the 72 study patients was 43.8 months with a median angle of deviation of 30 prism diopters (PD) at both distance and near. Ten patients (13.9%) required a second surgical procedure while one patient (1.4%) required a third. The cumulative probability of a second surgery within two years of the first procedure was 24% (95% CI 4–43%). During a median postoperative follow-up period of 7.1 months, 64 (88.9%) patients were within 8 PD of orthotropia on the last postoperative examination. Normal postoperative stereoacuity was achieved in several children whose deviation began after 30 months of age, as well as in one child who was misaligned for at least two years prior to surgery. Although the postoperative follow-up on these patients with acquired nonaccommodative esotropia managed without prism adaptation is short, the motor results are similar to other studies on patients with acquired esotropia, with sensory outcomes superior to those obtained in children with congenital esotropia.