Jay C. Erie

Conjunctival and Corneal Intraepithelial and Invasive Neoplasia

The histopathologic findings and clinical records of 98 patients with conjunctival and corneal intraepithelial neoplasia (CIN) and 22 patients with invasive neoplasia were studied. Pathologic material was evaluated for cell type, degree of dysplasia, margins of excision, and change in pattern with recurrence. Clinical records were reviewed for demographic features, presenting symptoms, clinical appearance, therapy, and subsequent course. Recurrences occurred in 23 patients with CIN and 9 patients with invasive neoplasia. Intraocular or orbital extensions or both occurred in four patients and metastatic disease in two patients. The cell type, clinical appearance, and degree of dysplasia did not correlate with recurrence; involvement of the margins of the initial excision was an important prognostic sign for recurrence.

Effect of myopic laser in situ keratomileusis on epithelial and stromal thickness: a confocal microscopy study.

PURPOSE To determine changes in central epithelial and stromal thickness in human corneas in vivo after laser in situ keratomileusis (LASIK). DESIGN Prospective, nonrandomized, comparative trial. PARTICIPANTS Eighteen eyes of 12 patients received LASIK (performed using the VISX Star laser [VISX, Santa Ana, CA]) with a planned 180- micro m flap (created using an automated Hansatome microkeratome [Bausch & Lomb, Irvine, CA]) to correct refractive errors between -2.0 diopters (D) and -11.0 D. METHODS Corneas were examined by using confocal microscopy in vivo before LASIK and at 1 week and 1, 3, 6, and 12 months after LASIK. Epithelial thickness was the distance between images of the surface epithelium and subbasal nerve plexus or, when nerves were not visible, the subbasal peak (if present in the light intensity profile). Total flap thickness was the distance between images of the surface epithelium and interface debris (or peak), and total stromal thickness was the distance between images of the most anterior keratocytes and endothelium. MAIN OUTCOME MEASURES Corneal epithelial and stromal thickness. RESULTS Epithelial thickness before LASIK was 46 +/- 5 micro m (mean +/- standard deviation) and increased 22% by 1 month after LASIK (56 +/- 5 micro m; P = 0.01). Thereafter, epithelial thickness did not change, but remained thicker at 12 months after LASIK (54 +/- 8 micro m) than before LASIK (P = 0.02). Total flap thickness at 1 month after LASIK was 160 +/-28 micro m and did not change thereafter. Changes in total stromal thickness between 1 and 12 months after LASIK were not significant. CONCLUSIONS The central corneal epithelium was thicker in the first year after LASIK than before LASIK. There was no change in central stromal thickness between 1 month and 12 months after LASIK.

Retinal detachment in Olmsted County, Minnesota, 1976 through 1995

Abstract Objective To estimate the incidence of rhegmatogenous retinal detachment (RD) in a geographically defined population and to compare the probability of RD in residents after cataract extraction with the probability of RD in residents who did not have cataract extraction. Design Rochester Epidemiology Project databases were used to perform a retrospective population-based incidence study of RD diagnosed between 1976 and 1995 with cohort analyses of the influence of risk factors on the occurrence of RD. Participants The population of Olmsted County, Minnesota, participated. Main outcome measure Incidence rates of RD adjusted to the age and gender distribution of the 1990 U.S. white population were measured. Results Three hundred eleven incident cases of rhegmatogenous RD were identified. The mean annual age- and gender-adjusted incidence rate of rhegmatogenous RD was 17.9 per 100,000 persons (95% confidence interval [CI], 15.9–19.9). For idiopathic rhegmatogenous RD alone, the mean annual age- and gender-adjusted incidence rate was 12.6 (95% CI, 10.9–14.3) per 100,000 persons. Ten years after phacoemulsification and extracapsular cataract extraction, the estimated cumulative probability of RD was 5.5 (95% CI, 3.4–7.6) times as high as would have been expected in a similar group of county residents not undergoing cataract surgery. Conclusions Cataract surgery is associated with a significantly elevated long-term cumulative probability of retinal detachment.

Confocal microscopy in ophthalmology.

PURPOSE To describe the principles, capabilities, and applications of confocal microscopy in vivo in ophthalmology. DESIGN Perspective, literature review, and commentary. METHODS Review and synthesis of selected recent literature, with interpretation and perspective. RESULTS Confocal microscopy imaging has led to a better understanding of the cellular microstructure in the normal, postsurgical, and diseased cornea by enabling quantitative analysis of the cellular response in the human cornea in vivo. At present, the major role of confocal microscopy is in research of corneal surgery and disease. Clinical applications are limited to facilitating the diagnosis of Acanthamoeba and deep fungal keratitis, measuring residual bed thickness after laser in situ keratomileusis, and measuring endothelial cell density in high-light-scattering situations. CONCLUSIONS In addition to providing qualitative data, confocal microscopy is valuable for quantitative analysis of the cornea and will enable the investigation of pharmacologic and surgical modifications of corneal wound healing, nerve regeneration, and cellular responses. Prospective, quantitative analyses require individual calibration of confocal microscopes for lateral and axial dimensions of images, for image depth, and for light intensity.

Keratocyte density in keratoconus. A confocal microscopy study

PURPOSE To estimate keratocyte density in human corneas with keratoconus by confocal microscopy. DESIGN Prospective, observational cohort study. METHODS Twenty-nine unscarred corneas of 19 patients with keratoconus and 29 corneas of 19 controls matched for age (+/-3 years) and contact lens wear were examined by using confocal microscopy. Images were recorded from the full-thickness central cornea. A masked observer manually counted bright objects (keratocyte nuclei) in images without motion blur. Cell densities in anteroposterior stromal layers of keratoconus corneas were compared with densities in corresponding layers of control corneas. RESULTS In keratoconus patients, age 40 +/- 15 years (mean +/- standard deviation), keratocyte density was 19% lower in those who wore contact lenses (16,894 +/- 4032 cell/mm(3), n = 12) than in those who did not wear contact lenses (20,827 +/- 4934 cell/mm(3), n = 17, P =.03). In control patients, age 39 +/- 16 years, there was no difference in keratocyte density between those who wore contact lenses (n = 12) and those who did not wear contact lenses (n = 17, P =.80). Among contact lens wearers, keratocyte density was 25% lower in keratoconus corneas (16,894 +/- 4, 032 cell/mm(3), n = 12 [9 = rigid gas-permeable lenses, 3 = soft lenses]) than in control corneas (22,579 +/- 2, 387 cell/mm(3), n = 12 [3 = rigid gas-permeable lenses, 9 = soft lenses], P =.002), the result of cell density being lower in the most anterior keratocyte layer (P =.001) and the layers between 0% to 10% (P <.001), 67% to 90% (P <.001), and 91% to 100% (P <.001) of stromal thickness. Among noncontact lens wearers, there was no difference in cell density between keratoconus and controls (P =.41). CONCLUSION Keratocyte density is decreased in the anterior and posterior stroma of keratoconus patients who wear contact lenses.

Keratocyte density of central human cornea after laser in situ keratomileusis

PURPOSE To determine changes in keratocyte density in the first year after laser in situ keratomileusis (LASIK). DESIGN Prospective interventional cohort study. METHODS Seventeen eyes of 11 patients received LASIK with a planned 180-microm flap to correct refractive errors between -2.0 diopters and -11.0 diopters. Images of the full-thickness cornea were obtained by using confocal microscopy in vivo before LASIK and at 1 week, 1, 3, 6, and 12 months after LASIK. Bright objects (that resembled keratocytes) in images without motion blur were manually counted by one observer. Cell densities were determined in anterior and posterior halves of the stromal flap, anterior and posterior halves of the layer 100 microm-thick immediately deep to the ablation (retroablation layer), and in the posterior third of the stroma. The region of stroma that was ablated (as measured 1 month after LASIK) was omitted from the preoperative analysis. RESULTS Keratocyte density in the anterior flap was 28,978 +/- 5849 cells/mm(3) (mean +/- SD) pre-LASIK, and was decreased at all postoperative examinations, but the difference was not significant until 12 months after LASIK (22% decrease). Keratocyte densities in the posterior flap were 20,397 +/- 4215 cells/mm(3) pre-LASIK and were decreased by 20%-40% at all postoperative examinations 1 week to 1 year after LASIK. Keratocyte densities in the anterior half of the retroablation layer were 16,605 +/- 3595 cells/mm(3) pre-LASIK and decreased by 16%-30% between 3 and 12 months after LASIK. Keratocyte densities in the posterior half of the retroablation layer and posterior stroma did not change. CONCLUSIONS Keratocyte densities in the posterior flap and anterior retroablation layer (regions adjacent to the lamellar cut) decrease at 1 week and 3 months, respectively, after LASIK and remain decreased in these regions at 12 months after LASIK. In the anterior flap, keratocyte density decreases 1 year after LASIK. The long-term effects of these cellular deficits, if any, require further study.

Incidence of cataract surgery from 1980 through 2004: 25-year population-based study

PURPOSE: To estimate sex‐ and age‐specific incidence rates of cataract surgery in a defined United States population and evaluate the change in incidence over time. SETTING: Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. METHODS: Rochester Epidemiology Project databases were used to identify all incident cataract surgeries in Olmsted County, Minnesota, residents during the 25‐year period from January 1, 1980, through December 31, 2004. Annual incidence rates for each sex and 10‐year age group were calculated and adjusted to the 2000 U.S. white population. Change in incidence over time was assessed by fitting generalized linear models assuming a Poisson error structure. RESULTS: During the study period, 10 245 cataract extractions were performed in 7141 residents of all ages. Overall, the age‐adjusted cataract surgery incident rate per 100 000 residents was 548 (95% confidence interval [CI], 534‐561) for women, 462 (95% CI, 447‐478) for men, and 511 (95% CI, 501‐521) for all residents. The incidence of cataract surgery increased 500% among women and 467% among men during the study period (P<.001). Overall, the incidence of cataract surgery was highest in residents 70 years and older (3538 surgeries [95% CI, 3322‐3764] per 100 000 residents). CONCLUSIONS: This population‐based study found a substantial increase in incident cataract surgery among Olmsted County residents during the 25‐year study period. The rate of cataract surgery increased in a nearly linear fashion during a period when phacoemulsification replaced extracapsular cataract extraction in the community.

The Effect of Age on the Corneal Subbasal Nerve Plexus

Purpose: To measure subbasal nerve density and orientation in normal human corneas across a broad age range. Methods: Sixty-five normal corneas of 65 subjects were examined by using tandem scanning confocal microscopy. Ages of subjects ranged from 15 to 79 years (mean 46 ± 19 years), with 5 subjects from each hemidecade. Subbasal nerve fiber bundles appeared as bright, well-defined linear structures in confocal images of the central cornea. Images from 3 to 8 scans per eye (mean 4.6 ± 1.8 scans) were randomly presented to a masked observer for analysis. The mean subbasal nerve density (total nerve length [μm] within a confocal image [area = 0.166 mm2]), the mean nerve number per confocal scan, and the mean nerve orientation were determined by using a custom software program. Correlations between age and nerve density and age and nerve orientation were assessed by using Pearson correlation coefficients. Results: The subbasal nerve plexus was visible in the central cornea of all subjects. The mean subbasal nerve density was 8404 ± 2012 μm/mm2 (range 4735 to 14,018 μm/mm2). The mean subbasal nerve number was 4.6 ± 1.6 nerves (range 1 to 8 nerves). The mean subbasal nerve orientation was 94 ± 16 degrees (range 58 to 146 degrees). There was no correlation between age and subbasal nerve density (r = 0.21, P = 0.09) or between age and subbasal nerve orientation (r = −0.19, P = 0.12). Conclusion: The density and orientation of the subbasal nerve plexus in the central human cornea does not change with age.

Analysis of postoperative glare and intraocular lens design

Purpose: To assess the potential for reflected glare images from commonly used intraocular lens (IOL) materials and designs. Setting: Mayo Clinic, Rochester, Minnesota, USA. Methods: The interaction of reflected light rays from 3 commonly used IOLs (Bausch & Lomb LI61U and P359UV; Alcon AcrySof® MA60BM) with different optic designs (equi‐biconvex: 10.0 and 15.0 mm anterior radius of curvature; unequal biconvex: 32.0 mm anterior radius of curvature) and optic materials (silicone, poly[methyl methacrylate], and acrylic) were examined in an eye model using the Zemax optical design program. The potential of each IOL model to produce subjective glare was determined from the size of the defocused reflected glare image at the retina. Results: The unequal biconvex design concentrated reflected light on a retinal area that was 60‐fold smaller than that of the equi‐biconvex design. Increasing the refractive index of the IOL material from 1.43 (silicone) to 1.55 (acrylic) increased the amount of reflected light 5‐fold. Compared to an equi‐biconvex design composed of a lower refractive index material, the unequal biconvex design with a higher refractive index material increased the relative intensity of reflected light at the retina 300‐fold, and for eyes with low corneal power the intensity increased 3500‐fold. Similarly, for external glare apparent to an outside observer, the intensity of reflected light increased 400‐fold and for low corneal power it increased 6000‐fold. Conclusion: An unequal biconvex IOL design (32.0 mm anterior radius of curvature) composed of a higher refractive index material increased the potential for postoperative glare and external reflections.

Increasing incidence of cataract surgery: Population-based study

Purpose To estimate the incidence of cataract surgery in a defined population and to determine longitudinal cataract surgery patterns. Setting Mayo Clinic, Rochester, Minnesota, USA. Design Cohort study. Methods Rochester Epidemiology Project (REP) databases were used to identify all incident cataract surgeries in Olmsted County, Minnesota, between January 1, 2005, and December 31, 2011. Age‐specific and sex‐specific incidence rates were calculated and adjusted to the 2010 United States white population. Data were merged with previous REP data (1980 to 2004) to assess temporal trends in cataract surgery. Change in the incidence over time was assessed by fitting generalized linear models assuming a Poisson error structure. The probability of second‐eye cataract surgery was calculated using the Kaplan‐Meier method. Results Included were 8012 cataract surgeries from 2005 through 2011. During this time, incident cataract surgery significantly increased (P<.001), peaking in 2011 with a rate of 1100 per 100 000 (95% confidence interval, 1050‐1160). The probability of second‐eye surgery 3, 12, and 24 months after first‐eye surgery was 60%, 76%, and 86%, respectively, a significant increase compared with the same intervals in the previous 7 years (1998 to 2004) (P<.001). When merged with 1980 to 2004 REP data, incident cataract surgery steadily increased over the past 3 decades (P<.001). Conclusion Incident cataract surgery steadily increased over the past 32 years and has not leveled off, as reported in Swedish population‐based series. Second‐eye surgery was performed sooner and more frequently, with 60% of residents having second‐eye surgery within 3 months of first‐eye surgery. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.