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Archives of Ophthalmology current issue

• Laser Photocoagulation, Photodynamic Therapy, and Intravitreal Bevacizumab for the Treatment of Juxtafoveal Choroidal Neovascularization Secondary to Pathologic Myopia [Clinical Sciences] :
  Objective  To compare the effects on visual acuity of laser treatment (LT), photodynamic therapy (PDT) with verteporfin, and intravitreal bevacizumab treatment in patients with juxtafoveal choroidal neovascularization secondary to pathologic myopia.Methods  This prospective randomized clinical investigation enrolled 54 patients, who were divided into 3 groups receiving PDT, LT, or intravitreal bevacizumab treatment. The anti–vascular endothelial growth factor group received 1.25 mg of intravitreal bevacizumab at baseline; retreatment was performed if persistent intraretinal or subretinal fluid evaluated on optical coherence tomography or if choroidal neovascularization progression was detected on fluorescein angiography. The PDT group received treatment following the Verteporfin in Photodynamic Therapy Study Group guidelines. The LT group was submitted to direct LT and received PDT treatment if subfoveal recurrence or progression was detected on fluorescein angiography. A change in best-corrected visual acuity was the primary outcome.Results  The mean best-corrected visual acuity in the PDT group decreased from 0.52 logMAR (SD, 0.24 logMAR) at baseline to 0.72 logMAR (SD, 0.25 logMAR) at the end of the study (P = .002). The LT group showed substantial stabilization from mean baseline visual acuity (mean, 0.45 logMAR [SD, 0.27 logMAR]) to the 24-month (mean, 0.56 logMAR [SD, 0.34 logMAR) examination values. The mean best-corrected visual acuity in the anti–vascular endothelial growth factor group increased from 0.6 logMAR (SD, 0.3 logMAR) at baseline to 0.42 logMAR (SD, 0.35 logMAR) at the end of the study (P = .006).Conclusions  Overall, bevacizumab treatment offers the best functional results during a 2-year follow-up. In view of the small size of the sample in this study and the relatively low frequency of juxtafoveal choroidal neovascularization secondary to pathologic myopia, a multicentric clinical trial is necessary to validate our results.Published online February 8, 2010 (doi:10.1001/archophthalmol.2009.408).
• About This Journal [About This Journal]
• Fixed Combination of Latanoprost and Timolol vs Individual Components for Primary Open-Angle Glaucoma or Ocular Hypertension: A Randomized, Double-Masked Study [Clinical Trial] :
  Objective  To assess the efficacy and safety of fixed-combination latanoprost-timolol (FCLT) vs latanoprost or timolol monotherapy. Methods  This 12-week, randomized, double-masked, parallel-group study included patients with open-angle glaucoma or ocular hypertension treated with a β-blocker and with baseline intraocular pressure (IOP) of 26 through 36 mm Hg. Following washout, eligible patients were randomized to once-daily FCLT in the evening, latanoprost in the evening, or timolol in the morning. Main Outcome Measures  Postbaseline IOP assessments at 8 am, 10 am, and 4 pm at weeks 2, 6, and 12; statistical superiority of FCLT for the 18 pairwise comparisons between FCLT and the 2 monotherapies, using analysis of variance. Results  All therapies resulted in significant IOP reductions from baseline. Pairwise comparisons favored FCLT at all time points. When the 18 comparisons were tested simultaneously, FCLT was statistically superior to latanoprost at 7 of 9 time points and at all 9 time points when compared with timolol. In addition, FCLT was associated with greater percentage reductions in diurnal IOP levels and a greater likelihood of achieving lower mean diurnal IOP levels. Diurnal IOP reductions of 30% or more from baseline to week 12 were achieved by 73.5%, 57.5%, and 32.8% of those treated with FCLT, latanoprost, and timolol, respectively (P = .007 for FCLT vs timolol; P < .001 for FCLT vs latanoprost). All therapies were well tolerated. Conclusions  Fixed-combination latanoprost-timolol therapy is as safe and effective in lowering IOP in patients with either ocular hypertension or glaucoma as monotherapy with latanoprost or timolol. Combination therapy can be used to treat patients for whom monotherapy does not provide sufficient IOP reduction. Application to Clinical Practice  The simplicity, efficacy, and tolerability of FCLT contribute to its utility in clinical practice. Trial Registration  clinicaltrials.gov Identifier NCT00277498
• Publishing Online Ahead of Print [Announcement]
• Immunohistochemical Studies of Conjunctival Nevi and Melanomas [Clinical Sciences] :
  Objective  To evaluate the role of immunohistochemical methods in the diagnosis of benign and malignant conjunctival melanocytic proliferations. Design  Retrospective immunohistopathologic study. Methods  Paraffin-embedded tissue sections from 20 conjunctival nevi and 15 invasive melanomas were immunoreacted with antibodies against cellular antigens S-100 protein, MART-1, HMB-45, CD-45, and Ki-67 nuclear proliferation protein. Results  All nevi immunostained moderately to strongly for S-100 protein and MART-1. Results for HMB-45 were negative in the middle and lower subepithelial portions of 18 of 20 lesions; it was usually only weakly positive within the superficial junctional zone. Only 1 melanoma did not stain positively for S-100; MART-1 and HMB-45 were positive in all lesions at some level of intensity. Ki-67 positivity was restricted to the junctional zone of nevi and was diffuse in melanomas. The mean Ki-67 proliferation indices were 1.89% for the nevi and 17.3% for the melanomas. CD-45 can help to highlight lymphocytes that immunostain with Ki-67. Melanomas in situ and atypical primary acquired melanoses had more than twice the Ki-67 proliferation counts of intraepithelial junctional nevocytes (P < .001) and more intense HMB-45 cytoplasmic staining than junctional zone nevocytes. Conclusions  S-100 and MART-1 were not useful in separating benign from malignant lesions. Results for nevus cells beneath the junctional zone were overwhelmingly negative for HMB-45 and Ki-67. Two nevi and all melanomatous nodules were positive for HMB-45 (P < .001). A higher Ki-67 proliferation index convincingly separated melanomas from nevi (P < .001). Immunostaining for HMB-45 and Ki-67 are valuable adjuncts to careful histopathologic evaluation in assessing benign and malignant conjunctival melanocytic tumors.
• New Insights Into Changes in Corneal Thickness in Healthy Mountaineers During a Very-High-Altitude Climb to Mount Muztagh Ata [Clinical Sciences] :
  Objective  To investigate the effect of very high altitude and different ascent profiles on central corneal thickness (CCT). Methods  Twenty-eight healthy mountaineers were randomly assigned to 2 different ascent profiles during a medical research expedition to Mount Muztagh Ata (7546 m) in western China. Group 1 was allotted a shorter acclimatization time prior to ascent to 6265 m. The main outcome measure was CCT. Secondary outcome measures were oxygen saturation (SpO₂) and symptom assessments of acute mountain sickness (cerebral acute mountain sickness score). Examinations were performed at 490, 4497, 5533, and 6265 m. Results  Central corneal thickness increased in both groups with increasing altitude and decreased after descent. In group 1 (with the shorter acclimatization), mean CCT increased from 537 to 572 µm. Mean CCT in group 2 increased from 534 to 563 µm (P = .048). The amount of decrease in SpO₂ paralleled the increase in CCT. There was no significant decrease in visual acuity. There was a significant correlation between CCT and cerebral acute mountain sickness score when controlled for SpO₂ and age. Conclusions  Corneal swelling during high-altitude climbs is promoted by low SpO₂. Systemic delivery of oxygen to the anterior chamber seems to play a greater role in corneal oxygenation than previously thought. Adhering to a slower ascent profile results in less corneal edema. Visual acuity in healthy corneas is not adversely affected by edema at altitudes of up to 6300 m. Individuals with more acute mountain sickness–related symptoms had thicker corneas, possibly due to their higher overall susceptibility to hypoxia.
• In Memoriam: Steven M. Podos, MD (1937-2009) [Obituary]
• Efficacy of Sustained Topical Dorzolamide Therapy for Cystic Macular Lesions in Patients With X-Linked Retinoschisis [Clinical Sciences] :
  Objective  To determine the efficacy of sustained topical therapy with dorzolamide hydrochloride, 2%, on visual acuity and cystic macular lesions in patients with juvenile X-linked retinoschisis (XLRS). Design  Retrospective analysis. Setting  University hospital, tertiary care referral center. Patients  Twenty-nine eyes of 15 patients with XLRS receiving treatment with the topical dorzolamide formulation for 4 to 41 months were enrolled. Main Outcome Measures  Changes in visual acuity, cystic macular lesions, and central foveal zone thickness on optical coherence tomography during follow-up for the duration of treatment. Results  Among the 15 patients with XLRS, 20 eyes (69%) of 11 patients showed a positive response to treatment. Five of the 20 eyes (25%) in 3 of the 11 patients showed an initial response and a subsequent rebound of macular cysts. In 4 eyes (14%) of 3 patients, there was no response to treatment, but the macular cysts did not worsen compared with the baseline level. In 5 additional eyes (17%) of 4 patients, there was no response to treatment, and the macular cysts worsened when compared with the baseline level. Sixteen eyes (55%) of 12 patients had improvement in best-corrected visual acuity by at least 7 letters in at least 1 eye at the most recent follow-up visit. Seventeen eyes (59%) of 10 patients showed a reduction in the central foveal zone thickness in at least 1 eye when compared with the pretreatment level. Conclusion  Patients with XLRS have the potential to experience a beneficial effect from sustained treatment with dorzolamide, 2%.
• Dr Thompson's Eye Water [Ophthalmological Ephemera]
• Relationship of Blood Pressure to Retinal Vessel Diameter in Type 1 Diabetes Mellitus [Clinical Sciences] :
  Objective  To examine the relationship of blood pressure (BP) and use of angiotensin-receptor blocker or angiotensin-converting enzyme inhibitor to retinal vessel diameter in normotensive, normoalbuminuric persons with type 1 diabetes mellitus. Methods  In a randomized, controlled clinical trial, clinic and 24-hour ambulatory BPs were measured in persons with type 1 diabetes mellitus and gradable fundus photographs both at baseline (n = 147) and at 5-year follow-up (n = 124). Retinal arteriole and venule diameters were measured by a computer-assisted technique. Individual arteriole and venule measurements were combined into summary indexes that reflect the average retinal arteriole (central retinal arteriole equivalent [CRAE]) and venule (central retinal venule equivalent [CRVE]) diameter of an eye, respectively. Results  While controlling for age, study site, glycosylated hemoglobin level, and ambulatory pulse rate, the daytime ambulatory systolic (–0.29-µm effect per 1 mm Hg; P = .02), daytime ambulatory diastolic (–0.44-µm effect per 1 mm Hg; P = .04), nighttime ambulatory systolic (–0.27-µm effect per 1 mm Hg; P = .03), and 24-hour ambulatory systolic (–0.31-µm effect per 1 mm Hg; P = .03) BPs were cross-sectionally associated with a smaller CRAE. While controlling for age, study site, glycosylated hemoglobin level, ambulatory pulse rate, and baseline CRAE, no BP measure was associated with a change in CRAE or CRVE during 5 years of follow-up. Treatment with losartan potassium or enalapril maleate was not associated with a statistically significant change in CRAE or CRVE. Conclusion  Angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker therapy does not affect retinal arteriole or venule diameter in normotensive persons with type 1 diabetes mellitus. Trial Registration  clinicaltrials.gov Identifier: NCT00143949
• Impact of Liver Transplantation on Transthyretin-Related Ocular Amyloidosis in Japanese Patients [Clinical Sciences] :
  Objective  To evaluate the long-term impact of liver transplantation on ocular manifestations of familial amyloid polyneuropathy (FAP) in Japanese patients. Methods  Medical records were retrospectively reviewed in a long-term follow-up study. Of 52 patients with FAP amyloidogenic transthyretin Val30Met, 22 patients underwent liver transplantation. We assessed ocular manifestations, including amyloid deposition at the pupillary border, pupillary border with irregularity, vitreous opacities, and glaucoma, in patients who underwent liver transplantation. In addition, we compared the clinical characteristics of vitreous opacities—the most common ocular manifestation of FAP—in patients who underwent liver transplantation and those who did not to determine the effect of transplantation on the progression of ocular amyloidosis. Results  Mean time after FAP onset was 10 years and after liver transplantation was 7 years in patients who underwent liver transplantation. All ocular manifestations increased with time after transplantation. Eight patients (36%) developed vitreous opacities and 4 patients (18%) developed glaucoma during follow-up. Mean time from FAP onset to vitreous opacities onset was significantly shorter in patients with early-onset disease who underwent liver transplantation than in those who did not. Conclusions  Patients with FAP who undergo liver transplantation continue to have a long-term risk of severe ocular manifestations, especially vitreous opacities and glaucoma, which can restrict their daily lives, even after liver transplantation.
• Development of Choroidal Neovascularization in Rats With Advanced Intense Cyclic Light-Induced Retinal Degeneration [Laboratory Sciences] :
  Objectives  To study the progressive changes of intense cyclic light–induced retinal degeneration and to determine whether it results in choroidal neovascularization (CNV). Methods  Albino rats were exposed to 12 hours of 3000-lux cyclic light for 1, 3, or 6 months. Fundus examination, fundus photography, fluorescein and indocyanine green angiography, and optical coherence tomography were performed prior to euthanization. Light-exposed animals were euthanized after 1, 3, or 6 months for histopathological evaluation. Retinas were examined for the presence of 4-hydroxy-2-nonenal– and nitrotyrosine-modified proteins by immunofluorescence staining. Results  Long-term intense cyclic light exposure resulted in retinal degeneration with loss of the outer segments of photoreceptors and approximately two-thirds of the outer nuclear layer as well as development of subretinal pigment epithelium neovascularization after 1 month. Almost the entire outer nuclear layer was absent with the presence of CNV, which penetrated the Bruch membrane and extended into the outer retina after 3 months. Absence of the outer nuclear layer, multiple foci of CNV, retinal pigment epithelial fibrous metaplasia, and connective tissue bands containing blood vessels extending into the retina were observed after 6 months. All intense light–exposed animals showed an increased presence of 4-hydroxy-2-nonenal and nitrotyrosine staining. Optical coherence tomographic and angiographic studies confirmed retinal thinning and leakiness of the newly formed blood vessels. Conclusions  Our results suggest that albino rats develop progressive stages of retinal degeneration and CNV after long-term intense cyclic light exposure, allowing the detailed study of the pathogenesis and treatment of age-related macular degeneration. Clinical Relevance  The ability to study the progressive pathogenesis of age-related macular degeneration and CNV will provide detailed knowledge about the disease and aid in the development of target-specific therapy.
• Expression of Vascular Endothelial Growth Factor in Retinoblastoma [Laboratory Sciences] :
  Objectives  To investigate the immunohistochemical expression of vascular endothelial growth factor (VEGF) and to determine its possible association with tumor differentiation status, optic nerve and/or choroidal invasion, anterior chamber invasion, vitreous seeding, and basophilic staining of the vascular walls. Methods  A retrospective study was performed to identify the expression of VEGF in 47 of 129 consecutive patients with retinoblastoma treated at the Ocular Pathology Laboratory of the Anatomy and Pathology Institute of the Central University of Venezuela in Caracas from January 1, 2000, through December 31, 2007. Results  A positive correlation between VEGF staining intensity and time of progression and mitotic and apoptotic indexes was observed. However, no correlation was found between VEGF expression and other prognostic factors in this malignant neoplasm, including tumor stage as assessed by the Grabowski and Abramson classification. Conclusions  Although the isolated characterization of VEGF in retinoblastoma is not grounds for this protein to be considered a prognostic factor, its association with mitotic and apoptotic indexes suggests it may play a role in the progression of this disease. Thus, therapeutic targeting of VEGF in retinoblastoma may be an effective strategy to reduce tumor progression.
• Rate of Endophthalmitis After Cataract Surgery in Quebec, Canada, 1996-2005 [Epidemiology] :
  Objective  To estimate the annual incidence of endophthalmitis after cataract surgery from January 1, 1996, through December 31, 2005, in Quebec, Canada. Methods  Deidentified data were obtained from an outpatient physician billing database (Quebec State Control for Health Insurance [RAMQ]) with regard to all cataract surgical procedures performed from January 1, 1996, through December 31, 2005, in Quebec. For this cohort, records of an International Classification of Diseases, Ninth Revision (ICD-9) code for endophthalmitis during the same years were requested from 2 sources: the RAMQ outpatient database and an inpatient hospital discharge database (Maintenance and Exploitation of Data for the Study of Hospitalized Patients [MED-ECHO]). Endophthalmitis after cataract surgery was assumed if it occurred within 90 days of the surgery. Risk factors were examined using ² tests and logistic regression. Results  After exclusions, 490 690 cataract surgical procedures were performed from January 1, 1996, through December 31, 2005. A total of 754 cases of endophthalmitis occurred within 90 days after surgery for an overall incidence rate of 1.5 per 1000 surgical procedures (95% confidence interval [CI], 1.4-1.7). Factors associated with endophthalmitis included age of 85 years or older (odds ratio [OR], 1.34; 95% CI, 1.06-1.70), male sex (1.44; 1.24-1.66), later year of surgery (0.94; 0.92-0.97), and region of cataract surgery, because regions 6 (2.21; 1.91-2.55) and 9 (4.00; 2.48-6.43) had higher rates compared with all other regions. Conclusion  Reasons that explain the apparent decrease in endophthalmitis, especially in 2005, should be explored and further research performed to understand why certain patients and regions have higher risks of endophthalmitis after cataract surgery.
• Association Between the Use of Glaucoma Medications and Mortality [Socioeconomics and Health Services] :
  Objective  To evaluate the relationship between glaucoma medication use and death. Methods  This study uses longitudinal data from 2003 to 2007 on persons 40 years and older with glaucoma or suspected glaucoma enrolled in a large managed care network. Cox regression analysis was performed to estimate the hazard of death associated with the use of various glaucoma medication classes and combinations thereof. Multivariable models were adjusted for demographic characteristics and comorbid medical conditions. Results  Of 21 506 participants with glaucoma or suspected glaucoma, 237 (1.1%) died during the study period. The use of any class of glaucoma medication was associated with a 74% reduced hazard of death (adjusted hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.16-0.40) compared with no glaucoma medication use. This association was observed for use of a single agent alone, such as a topical β-antagonist (0.44; 0.24-0.83) or a prostaglandin analogue (0.31; 0.18-0.54), and for use of different combinations of drug classes. Conclusions  After adjustment for potential confounding variables, the use of glaucoma medications was associated with a reduced likelihood of death in this large sample of US adults with glaucoma. Future investigations should explore this association further because these findings may have important clinical implications.
• Harvesting Fresh Tumor Tissue From Enucleated Eyes: The 2008 Jack S. Guyton Lecture [Surgical Technique] :
  There is an increasing need to obtain fresh tumor tissue and normal tissue for genetic studies and research following enucleation of an eye for uveal melanoma, retinoblastoma, and other lesions. A concern about doing this is that the globe will often collapse and lead to difficulties with gross and histopathologic interpretation. The technique reported herein is based on the creation of an opening in the sclera using an 8-mm corneal trephine followed by removal of tumor tissue. This method provides adequate tissue, preserves the spherical configuration of the eye, and allows for excellent histopathologic sections.
• Intense Cyclic Light-Induced Retinal Degeneration in Rats [Editorial]
• Moving Toward Information in the Blink of an Eye [Editorial]
• Kindred With Prominent Corneal Nerves Associated With a Mutation in Codon 804 of RET on Chromosome 10q11 [Small Case Series]
• Intravitreous Ranibizumab (Lucentis) for Radiation Maculopathy [Small Case Series]

Archives of Opthalmology recent issues

• Laser Photocoagulation, Photodynamic Therapy, and Intravitreal Bevacizumab for the Treatment of Juxtafoveal Choroidal Neovascularization Secondary to Pathologic Myopia [Clinical Sciences] :
  Objective  To compare the effects on visual acuity of laser treatment (LT), photodynamic therapy (PDT) with verteporfin, and intravitreal bevacizumab treatment in patients with juxtafoveal choroidal neovascularization secondary to pathologic myopia.Methods  This prospective randomized clinical investigation enrolled 54 patients, who were divided into 3 groups receiving PDT, LT, or intravitreal bevacizumab treatment. The anti–vascular endothelial growth factor group received 1.25 mg of intravitreal bevacizumab at baseline; retreatment was performed if persistent intraretinal or subretinal fluid evaluated on optical coherence tomography or if choroidal neovascularization progression was detected on fluorescein angiography. The PDT group received treatment following the Verteporfin in Photodynamic Therapy Study Group guidelines. The LT group was submitted to direct LT and received PDT treatment if subfoveal recurrence or progression was detected on fluorescein angiography. A change in best-corrected visual acuity was the primary outcome.Results  The mean best-corrected visual acuity in the PDT group decreased from 0.52 logMAR (SD, 0.24 logMAR) at baseline to 0.72 logMAR (SD, 0.25 logMAR) at the end of the study (P = .002). The LT group showed substantial stabilization from mean baseline visual acuity (mean, 0.45 logMAR [SD, 0.27 logMAR]) to the 24-month (mean, 0.56 logMAR [SD, 0.34 logMAR) examination values. The mean best-corrected visual acuity in the anti–vascular endothelial growth factor group increased from 0.6 logMAR (SD, 0.3 logMAR) at baseline to 0.42 logMAR (SD, 0.35 logMAR) at the end of the study (P = .006).Conclusions  Overall, bevacizumab treatment offers the best functional results during a 2-year follow-up. In view of the small size of the sample in this study and the relatively low frequency of juxtafoveal choroidal neovascularization secondary to pathologic myopia, a multicentric clinical trial is necessary to validate our results.Published online February 8, 2010 (doi:10.1001/archophthalmol.2009.408).
• About This Journal [About This Journal]
• Fixed Combination of Latanoprost and Timolol vs Individual Components for Primary Open-Angle Glaucoma or Ocular Hypertension: A Randomized, Double-Masked Study [Clinical Trial] :
  Objective  To assess the efficacy and safety of fixed-combination latanoprost-timolol (FCLT) vs latanoprost or timolol monotherapy. Methods  This 12-week, randomized, double-masked, parallel-group study included patients with open-angle glaucoma or ocular hypertension treated with a β-blocker and with baseline intraocular pressure (IOP) of 26 through 36 mm Hg. Following washout, eligible patients were randomized to once-daily FCLT in the evening, latanoprost in the evening, or timolol in the morning. Main Outcome Measures  Postbaseline IOP assessments at 8 am, 10 am, and 4 pm at weeks 2, 6, and 12; statistical superiority of FCLT for the 18 pairwise comparisons between FCLT and the 2 monotherapies, using analysis of variance. Results  All therapies resulted in significant IOP reductions from baseline. Pairwise comparisons favored FCLT at all time points. When the 18 comparisons were tested simultaneously, FCLT was statistically superior to latanoprost at 7 of 9 time points and at all 9 time points when compared with timolol. In addition, FCLT was associated with greater percentage reductions in diurnal IOP levels and a greater likelihood of achieving lower mean diurnal IOP levels. Diurnal IOP reductions of 30% or more from baseline to week 12 were achieved by 73.5%, 57.5%, and 32.8% of those treated with FCLT, latanoprost, and timolol, respectively (P = .007 for FCLT vs timolol; P < .001 for FCLT vs latanoprost). All therapies were well tolerated. Conclusions  Fixed-combination latanoprost-timolol therapy is as safe and effective in lowering IOP in patients with either ocular hypertension or glaucoma as monotherapy with latanoprost or timolol. Combination therapy can be used to treat patients for whom monotherapy does not provide sufficient IOP reduction. Application to Clinical Practice  The simplicity, efficacy, and tolerability of FCLT contribute to its utility in clinical practice. Trial Registration  clinicaltrials.gov Identifier NCT00277498
• Publishing Online Ahead of Print [Announcement]
• Immunohistochemical Studies of Conjunctival Nevi and Melanomas [Clinical Sciences] :
  Objective  To evaluate the role of immunohistochemical methods in the diagnosis of benign and malignant conjunctival melanocytic proliferations. Design  Retrospective immunohistopathologic study. Methods  Paraffin-embedded tissue sections from 20 conjunctival nevi and 15 invasive melanomas were immunoreacted with antibodies against cellular antigens S-100 protein, MART-1, HMB-45, CD-45, and Ki-67 nuclear proliferation protein. Results  All nevi immunostained moderately to strongly for S-100 protein and MART-1. Results for HMB-45 were negative in the middle and lower subepithelial portions of 18 of 20 lesions; it was usually only weakly positive within the superficial junctional zone. Only 1 melanoma did not stain positively for S-100; MART-1 and HMB-45 were positive in all lesions at some level of intensity. Ki-67 positivity was restricted to the junctional zone of nevi and was diffuse in melanomas. The mean Ki-67 proliferation indices were 1.89% for the nevi and 17.3% for the melanomas. CD-45 can help to highlight lymphocytes that immunostain with Ki-67. Melanomas in situ and atypical primary acquired melanoses had more than twice the Ki-67 proliferation counts of intraepithelial junctional nevocytes (P < .001) and more intense HMB-45 cytoplasmic staining than junctional zone nevocytes. Conclusions  S-100 and MART-1 were not useful in separating benign from malignant lesions. Results for nevus cells beneath the junctional zone were overwhelmingly negative for HMB-45 and Ki-67. Two nevi and all melanomatous nodules were positive for HMB-45 (P < .001). A higher Ki-67 proliferation index convincingly separated melanomas from nevi (P < .001). Immunostaining for HMB-45 and Ki-67 are valuable adjuncts to careful histopathologic evaluation in assessing benign and malignant conjunctival melanocytic tumors.
• New Insights Into Changes in Corneal Thickness in Healthy Mountaineers During a Very-High-Altitude Climb to Mount Muztagh Ata [Clinical Sciences] :
  Objective  To investigate the effect of very high altitude and different ascent profiles on central corneal thickness (CCT). Methods  Twenty-eight healthy mountaineers were randomly assigned to 2 different ascent profiles during a medical research expedition to Mount Muztagh Ata (7546 m) in western China. Group 1 was allotted a shorter acclimatization time prior to ascent to 6265 m. The main outcome measure was CCT. Secondary outcome measures were oxygen saturation (SpO₂) and symptom assessments of acute mountain sickness (cerebral acute mountain sickness score). Examinations were performed at 490, 4497, 5533, and 6265 m. Results  Central corneal thickness increased in both groups with increasing altitude and decreased after descent. In group 1 (with the shorter acclimatization), mean CCT increased from 537 to 572 µm. Mean CCT in group 2 increased from 534 to 563 µm (P = .048). The amount of decrease in SpO₂ paralleled the increase in CCT. There was no significant decrease in visual acuity. There was a significant correlation between CCT and cerebral acute mountain sickness score when controlled for SpO₂ and age. Conclusions  Corneal swelling during high-altitude climbs is promoted by low SpO₂. Systemic delivery of oxygen to the anterior chamber seems to play a greater role in corneal oxygenation than previously thought. Adhering to a slower ascent profile results in less corneal edema. Visual acuity in healthy corneas is not adversely affected by edema at altitudes of up to 6300 m. Individuals with more acute mountain sickness–related symptoms had thicker corneas, possibly due to their higher overall susceptibility to hypoxia.
• In Memoriam: Steven M. Podos, MD (1937-2009) [Obituary]
• Efficacy of Sustained Topical Dorzolamide Therapy for Cystic Macular Lesions in Patients With X-Linked Retinoschisis [Clinical Sciences] :
  Objective  To determine the efficacy of sustained topical therapy with dorzolamide hydrochloride, 2%, on visual acuity and cystic macular lesions in patients with juvenile X-linked retinoschisis (XLRS). Design  Retrospective analysis. Setting  University hospital, tertiary care referral center. Patients  Twenty-nine eyes of 15 patients with XLRS receiving treatment with the topical dorzolamide formulation for 4 to 41 months were enrolled. Main Outcome Measures  Changes in visual acuity, cystic macular lesions, and central foveal zone thickness on optical coherence tomography during follow-up for the duration of treatment. Results  Among the 15 patients with XLRS, 20 eyes (69%) of 11 patients showed a positive response to treatment. Five of the 20 eyes (25%) in 3 of the 11 patients showed an initial response and a subsequent rebound of macular cysts. In 4 eyes (14%) of 3 patients, there was no response to treatment, but the macular cysts did not worsen compared with the baseline level. In 5 additional eyes (17%) of 4 patients, there was no response to treatment, and the macular cysts worsened when compared with the baseline level. Sixteen eyes (55%) of 12 patients had improvement in best-corrected visual acuity by at least 7 letters in at least 1 eye at the most recent follow-up visit. Seventeen eyes (59%) of 10 patients showed a reduction in the central foveal zone thickness in at least 1 eye when compared with the pretreatment level. Conclusion  Patients with XLRS have the potential to experience a beneficial effect from sustained treatment with dorzolamide, 2%.
• Dr Thompson's Eye Water [Ophthalmological Ephemera]
• Relationship of Blood Pressure to Retinal Vessel Diameter in Type 1 Diabetes Mellitus [Clinical Sciences] :
  Objective  To examine the relationship of blood pressure (BP) and use of angiotensin-receptor blocker or angiotensin-converting enzyme inhibitor to retinal vessel diameter in normotensive, normoalbuminuric persons with type 1 diabetes mellitus. Methods  In a randomized, controlled clinical trial, clinic and 24-hour ambulatory BPs were measured in persons with type 1 diabetes mellitus and gradable fundus photographs both at baseline (n = 147) and at 5-year follow-up (n = 124). Retinal arteriole and venule diameters were measured by a computer-assisted technique. Individual arteriole and venule measurements were combined into summary indexes that reflect the average retinal arteriole (central retinal arteriole equivalent [CRAE]) and venule (central retinal venule equivalent [CRVE]) diameter of an eye, respectively. Results  While controlling for age, study site, glycosylated hemoglobin level, and ambulatory pulse rate, the daytime ambulatory systolic (–0.29-µm effect per 1 mm Hg; P = .02), daytime ambulatory diastolic (–0.44-µm effect per 1 mm Hg; P = .04), nighttime ambulatory systolic (–0.27-µm effect per 1 mm Hg; P = .03), and 24-hour ambulatory systolic (–0.31-µm effect per 1 mm Hg; P = .03) BPs were cross-sectionally associated with a smaller CRAE. While controlling for age, study site, glycosylated hemoglobin level, ambulatory pulse rate, and baseline CRAE, no BP measure was associated with a change in CRAE or CRVE during 5 years of follow-up. Treatment with losartan potassium or enalapril maleate was not associated with a statistically significant change in CRAE or CRVE. Conclusion  Angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker therapy does not affect retinal arteriole or venule diameter in normotensive persons with type 1 diabetes mellitus. Trial Registration  clinicaltrials.gov Identifier: NCT00143949
• Impact of Liver Transplantation on Transthyretin-Related Ocular Amyloidosis in Japanese Patients [Clinical Sciences] :
  Objective  To evaluate the long-term impact of liver transplantation on ocular manifestations of familial amyloid polyneuropathy (FAP) in Japanese patients. Methods  Medical records were retrospectively reviewed in a long-term follow-up study. Of 52 patients with FAP amyloidogenic transthyretin Val30Met, 22 patients underwent liver transplantation. We assessed ocular manifestations, including amyloid deposition at the pupillary border, pupillary border with irregularity, vitreous opacities, and glaucoma, in patients who underwent liver transplantation. In addition, we compared the clinical characteristics of vitreous opacities—the most common ocular manifestation of FAP—in patients who underwent liver transplantation and those who did not to determine the effect of transplantation on the progression of ocular amyloidosis. Results  Mean time after FAP onset was 10 years and after liver transplantation was 7 years in patients who underwent liver transplantation. All ocular manifestations increased with time after transplantation. Eight patients (36%) developed vitreous opacities and 4 patients (18%) developed glaucoma during follow-up. Mean time from FAP onset to vitreous opacities onset was significantly shorter in patients with early-onset disease who underwent liver transplantation than in those who did not. Conclusions  Patients with FAP who undergo liver transplantation continue to have a long-term risk of severe ocular manifestations, especially vitreous opacities and glaucoma, which can restrict their daily lives, even after liver transplantation.
• Development of Choroidal Neovascularization in Rats With Advanced Intense Cyclic Light-Induced Retinal Degeneration [Laboratory Sciences] :
  Objectives  To study the progressive changes of intense cyclic light–induced retinal degeneration and to determine whether it results in choroidal neovascularization (CNV). Methods  Albino rats were exposed to 12 hours of 3000-lux cyclic light for 1, 3, or 6 months. Fundus examination, fundus photography, fluorescein and indocyanine green angiography, and optical coherence tomography were performed prior to euthanization. Light-exposed animals were euthanized after 1, 3, or 6 months for histopathological evaluation. Retinas were examined for the presence of 4-hydroxy-2-nonenal– and nitrotyrosine-modified proteins by immunofluorescence staining. Results  Long-term intense cyclic light exposure resulted in retinal degeneration with loss of the outer segments of photoreceptors and approximately two-thirds of the outer nuclear layer as well as development of subretinal pigment epithelium neovascularization after 1 month. Almost the entire outer nuclear layer was absent with the presence of CNV, which penetrated the Bruch membrane and extended into the outer retina after 3 months. Absence of the outer nuclear layer, multiple foci of CNV, retinal pigment epithelial fibrous metaplasia, and connective tissue bands containing blood vessels extending into the retina were observed after 6 months. All intense light–exposed animals showed an increased presence of 4-hydroxy-2-nonenal and nitrotyrosine staining. Optical coherence tomographic and angiographic studies confirmed retinal thinning and leakiness of the newly formed blood vessels. Conclusions  Our results suggest that albino rats develop progressive stages of retinal degeneration and CNV after long-term intense cyclic light exposure, allowing the detailed study of the pathogenesis and treatment of age-related macular degeneration. Clinical Relevance  The ability to study the progressive pathogenesis of age-related macular degeneration and CNV will provide detailed knowledge about the disease and aid in the development of target-specific therapy.
• Expression of Vascular Endothelial Growth Factor in Retinoblastoma [Laboratory Sciences] :
  Objectives  To investigate the immunohistochemical expression of vascular endothelial growth factor (VEGF) and to determine its possible association with tumor differentiation status, optic nerve and/or choroidal invasion, anterior chamber invasion, vitreous seeding, and basophilic staining of the vascular walls. Methods  A retrospective study was performed to identify the expression of VEGF in 47 of 129 consecutive patients with retinoblastoma treated at the Ocular Pathology Laboratory of the Anatomy and Pathology Institute of the Central University of Venezuela in Caracas from January 1, 2000, through December 31, 2007. Results  A positive correlation between VEGF staining intensity and time of progression and mitotic and apoptotic indexes was observed. However, no correlation was found between VEGF expression and other prognostic factors in this malignant neoplasm, including tumor stage as assessed by the Grabowski and Abramson classification. Conclusions  Although the isolated characterization of VEGF in retinoblastoma is not grounds for this protein to be considered a prognostic factor, its association with mitotic and apoptotic indexes suggests it may play a role in the progression of this disease. Thus, therapeutic targeting of VEGF in retinoblastoma may be an effective strategy to reduce tumor progression.
• Rate of Endophthalmitis After Cataract Surgery in Quebec, Canada, 1996-2005 [Epidemiology] :
  Objective  To estimate the annual incidence of endophthalmitis after cataract surgery from January 1, 1996, through December 31, 2005, in Quebec, Canada. Methods  Deidentified data were obtained from an outpatient physician billing database (Quebec State Control for Health Insurance [RAMQ]) with regard to all cataract surgical procedures performed from January 1, 1996, through December 31, 2005, in Quebec. For this cohort, records of an International Classification of Diseases, Ninth Revision (ICD-9) code for endophthalmitis during the same years were requested from 2 sources: the RAMQ outpatient database and an inpatient hospital discharge database (Maintenance and Exploitation of Data for the Study of Hospitalized Patients [MED-ECHO]). Endophthalmitis after cataract surgery was assumed if it occurred within 90 days of the surgery. Risk factors were examined using ² tests and logistic regression. Results  After exclusions, 490 690 cataract surgical procedures were performed from January 1, 1996, through December 31, 2005. A total of 754 cases of endophthalmitis occurred within 90 days after surgery for an overall incidence rate of 1.5 per 1000 surgical procedures (95% confidence interval [CI], 1.4-1.7). Factors associated with endophthalmitis included age of 85 years or older (odds ratio [OR], 1.34; 95% CI, 1.06-1.70), male sex (1.44; 1.24-1.66), later year of surgery (0.94; 0.92-0.97), and region of cataract surgery, because regions 6 (2.21; 1.91-2.55) and 9 (4.00; 2.48-6.43) had higher rates compared with all other regions. Conclusion  Reasons that explain the apparent decrease in endophthalmitis, especially in 2005, should be explored and further research performed to understand why certain patients and regions have higher risks of endophthalmitis after cataract surgery.
• Association Between the Use of Glaucoma Medications and Mortality [Socioeconomics and Health Services] :
  Objective  To evaluate the relationship between glaucoma medication use and death. Methods  This study uses longitudinal data from 2003 to 2007 on persons 40 years and older with glaucoma or suspected glaucoma enrolled in a large managed care network. Cox regression analysis was performed to estimate the hazard of death associated with the use of various glaucoma medication classes and combinations thereof. Multivariable models were adjusted for demographic characteristics and comorbid medical conditions. Results  Of 21 506 participants with glaucoma or suspected glaucoma, 237 (1.1%) died during the study period. The use of any class of glaucoma medication was associated with a 74% reduced hazard of death (adjusted hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.16-0.40) compared with no glaucoma medication use. This association was observed for use of a single agent alone, such as a topical β-antagonist (0.44; 0.24-0.83) or a prostaglandin analogue (0.31; 0.18-0.54), and for use of different combinations of drug classes. Conclusions  After adjustment for potential confounding variables, the use of glaucoma medications was associated with a reduced likelihood of death in this large sample of US adults with glaucoma. Future investigations should explore this association further because these findings may have important clinical implications.
• Harvesting Fresh Tumor Tissue From Enucleated Eyes: The 2008 Jack S. Guyton Lecture [Surgical Technique] :
  There is an increasing need to obtain fresh tumor tissue and normal tissue for genetic studies and research following enucleation of an eye for uveal melanoma, retinoblastoma, and other lesions. A concern about doing this is that the globe will often collapse and lead to difficulties with gross and histopathologic interpretation. The technique reported herein is based on the creation of an opening in the sclera using an 8-mm corneal trephine followed by removal of tumor tissue. This method provides adequate tissue, preserves the spherical configuration of the eye, and allows for excellent histopathologic sections.
• Intense Cyclic Light-Induced Retinal Degeneration in Rats [Editorial]
• Moving Toward Information in the Blink of an Eye [Editorial]
• Kindred With Prominent Corneal Nerves Associated With a Mutation in Codon 804 of RET on Chromosome 10q11 [Small Case Series]
• Intravitreous Ranibizumab (Lucentis) for Radiation Maculopathy [Small Case Series]

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