Prevalence of corneal astigmatism before cataract surgery in Chinese patients

Purpose: To assess the demographics and distribution of corneal astigmatism before cataract surgery in Chinese patients. Setting: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. Design: Clinic-based cross-sectional study. Methods: From July 2009 to May 2011, preoperative bilateral partial coherence interferometry (IOLMaster) was performed in consecutive patients having cataract surgery. Patient demographics and keratometric data were recorded. Results: The mean age of the 2849 patients (4831 eyes) was 70.56 years ± 9.55 (SD); there was a predominance of women patients (64.0%). The mean axial length was 23.58 ± 1.13 mm. The mean corneal astigmatism in this cohort was 1.01 D (range 0.05 to 6.59 D). Corneal astigmatism was between 0.25 D and 1.25 D in 67.7% of eyes, 1.25 D or higher in 27.5% eyes, and less than 0.25 D in 4.8% of eyes. Astigmatism was with the rule in 25.1% of eyes, against the rule (ATR) in 58.2% of eyes, and oblique in 16.7% of eyes. The mean steep keratometry measurement was 44.76 ± 1.56 D. Against-the-rule astigmatism increased significantly with older age. Conclusions: Corneal astigmatism largely fell between 0.25 D and 1.25 D in these predominantly elderly female Chinese patients, and ATR astigmatism increased with age. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. © 2012 ASCRS and ESCRS.

Corneal complications associated with topical ophthalmic use of nonsteroidal antiinflammatory drugs.

PURPOSE:

To explore the potential association between adverse corneal events and the use of topical nonsteroidal antiinflammatory drugs (NSAIDs).

SETTING:

Practice-based reports.

METHODS:

A detailed case-reporting form and request for medical records were sent to all practices reporting cases of corneal or conjunctival pathology in association with the use of topical NSAIDs to the American Society of Cataract and Refractive Surgery. Cases were classified as "mild," "moderate," or "severe" according to predetermined clinical criteria.

RESULTS:

Records of 140 eyes (129 patients) were reviewed; 51 cases (36.4%) were mild, 55 (39.3%) moderate, and 34 (24.3%) severe. An association with a specific topical NSAID was confirmed in 117 cases (81.8%). Most confirmed cases (53.8%) involved generic diclofenac (Falcon). Cases associated with brand diclofenac (Voltaren, CIBA Vision) and ketorolac (Acular, Allergan) were more likely to have ocular comorbidity and to have received significantly higher total doses of NSAIDs. Neither "off-label" use nor use of any specific agent was associated with severe compared to mild or moderate disease. However, patients with more severe adverse events were more likely to have a history of diabetes, previous surgery in the affected eye, and surgery other than cataract. Cases not occurring in the perioperative period had significantly worse outcomes, had significantly more ocular comorbidities, and received nearly 3 times the dose of NSAIDs.

CONCLUSIONS:

While topical NSAIDs as a class may be associated with severe adverse events, such events appeared to require potentiation in the form of high total doses, ocular comorbidities, or both with Acular and Voltaren. Severe adverse events might have been more likely to occur at lower doses and in routine postoperative settings with generic diclofenac.

Central corneal thickness and corneal hysteresis associated with glaucoma damage.

PURPOSE:

We sought to measure the impact of central corneal thickness (CCT), a possible risk factor for glaucoma damage, and corneal hysteresis, a proposed measure of corneal resistance to deformation, on various indicators of glaucoma damage.

DESIGN:

Observational study.

METHODS:

Adult patients of the Wilmer Glaucoma Service underwent measurement of hysteresis on the Reichert Ocular Response Analyzer and measurement of CCT by ultrasonic pachymetry. Two glaucoma specialists (H.A.Q., N.G.C.) reviewed the chart to determine highest known intraocular pressure (IOP), target IOP, diagnosis, years with glaucoma, cup-to-disk ratio (CDR), mean defect (MD), pattern standard deviation (PSD), glaucoma hemifield test (GHT), and presence or absence of visual field progression.

RESULTS:

Among 230 subjects, the mean age was 65 +/- 14 years, 127 (55%) were female, 161 (70%) were white, and 194 (85%) had a diagnosis of primary open-angle glaucoma (POAG) or suspected POAG. In multivariate generalized estimating equation models, lower corneal hysteresis value (P = .03), but not CCT, was associated with visual field progression. When axial length was included in the model, hysteresis was not a significant risk factor (P = .09). A thinner CCT (P = .02), but not hysteresis, was associated with a higher CDR at the most recent examination. Neither CCT nor hysteresis was associated with MD, PSD, or GHT "outside normal limits."

CONCLUSIONS:

Thinner CCT was associated with the state of glaucoma damage as indicated by CDR. Axial length and corneal hysteresis were associated with progressive field worsening.

Corneal structure and biomechanics: impact on the diagnosis and management of glaucoma.

PURPOSE OF REVIEW:

Highlights recent studies relating to the impact of corneal structure and biomechanical properties on glaucoma evaluation and management.

RECENT FINDINGS:

Central corneal thickness has been shown to play a role in the interpretation of intraocular pressure. Central corneal thickness has also been suggested as a glaucoma risk factor. The potential role of other corneal factors, such as stromal makeup, in the accurate measurement of intraocular pressure and the assessment of glaucoma risk remains to be determined.

SUMMARY:

Improved understanding of central corneal thickness and corneal biomechanical properties may someday lead to a better understanding of glaucoma risk and its assessment.

Influence of corneal structure, corneal responsiveness, and other ocular parameters on tonometric measurement of intraocular pressure.

PURPOSE: To estimate the relationships between ocular parameters and tonometrically measured intraocular pressure (IOP), to determine the influence of ocular parameters on different instrument measurements of IOP, and to evaluate the association of ocular parameters with a parameter called hysteresis. METHODS: Patients presenting at a glaucoma clinic were recruited for this study. Subjects underwent IOP measurement with the Goldmann applanation tonometer (GAT), the TonoPen, and the Reichert Ocular Response Analyzer (ORA), and also measurements of central corneal thickness (CCT), axial length, corneal curvature, corneal astigmatism, central visual acuity, and refractive error. Chart information was reviewed to determine glaucoma treatment history. The ORA instrument provided a measurement called corneal hysteresis. The association between measured IOP and the other ocular characteristics was estimated using generalized estimating equations. RESULTS: Among 230 patients, IOP measurements from the TonoPen read lowest, and ORA read highest, and GAT measurements were closest to the mean IOP of the 3 instruments. In a multiple regression model adjusting for age, sex, race, and other ocular characteristics, a 10 microm increase in CCT was associated with an increase of 0.79 mm Hg measured IOP in untreated eyes (P<0.0001). Of the 3 tonometers, GAT was the least affected by CCT (0.66 mm Hg/10 mum, P<0.0001). Hysteresis was significantly correlated with CCT with a modest correlation coefficient (r=0.20, P<0.0007). CONCLUSIONS: Among parameters related to measured IOP, features in addition to CCT, such as hysteresis and corneal curvature, may also be important. Tonometric instruments seem to be affected differently by various physiologic characteristics.

Corneal hysteresis and axial length among Chinese secondary school children: the Xichang Pediatric Refractive Error Study (X-PRES) report no. 4.

PURPOSE: To evaluate the association between corneal hysteresis and axial length/refractive error among rural Chinese secondary school children. DESIGN: Cross-sectional cohort study. METHODS: Refractive error (cycloplegic auto-refraction with subjective refinement), central corneal thickness (CCT) and axial length (ultrasonic measurement), intraocular pressure (IOP), and corneal hysteresis (Reichert Ocular Response Analyzer) were measured on a rural school-based cohort of children. RESULTS: Among 1,233 examined children, the mean age was 14.7 +/- 0.8 years and 699 (56.7%) were girls. The mean spherical equivalent (n = 1,232) was -2.2 +/- 1.6 diopters (D), axial length (n = 643) was 23.7 +/- 1.1 mm, corneal hysteresis (n = 1,153) was 10.7 +/- 1.6 mm Hg, IOP (n = 1,153) was 17.0 +/- 3.4 mm Hg, and CCT (n = 1,226) was 553 +/- 33 microns. In linear regression models, longer axial length was significantly (P < .001 for both) associated with lower corneal hysteresis and higher IOP. Hysteresis in this population was significantly (P < .001) lower than has previously been reported for normal White children (n = 42, 12.3 +/- 1.3 mm Hg), when adjusting for age and gender. This difference did not appear to depend on differences in axial length between the populations, as it persists when only Chinese children with normal uncorrected vision are included. CONCLUSIONS: Prospective studies will be needed to determine if low hysteresis places eyes at risk for axial elongation secondary or if primary elongation results in lower hysteresis.

Corneal biomechanics, refractive error, and axial length in Chinese primary school children.

PURPOSE: Low corneal hysteresis is associated with longer axial length in Chinese secondary school children. The authors sought to explore this association in primary school children. METHODS: LogMAR presenting visual acuity, cycloplegic refractive error, ocular biometry, central corneal thickness (CCT), and corneal hysteresis (CH) was assessed for children in grades 1 to 3 at an academically competitive urban school in Shantou, China. RESULTS: Among 872 eligible children (mean age, 8.6 ± 2.1 years), 651 (74.7%) completed the examination. Among 1299 examined eyes, 111 (8.5%) had uncorrected vision ≤6/12. Mean spherical equivalent refractive error for all eyes was +0.26 ± 1.41 D, and axial length (AL) was 22.7 ± 0.90 mm. CH for the lowest (mean AL, 21.7 ± 0.39 mm), two middle (mean AL, 22.4 ± 0.15 and 22.9 ± 0.15 mm), and highest quartiles (mean AL, 23.7 ± 0.74 mm) of AL were 10.6 ± 2.1 mm Hg, 10.4 ± 2.1 mm Hg, 10.3 ± 2.3 mm Hg, and 10.2 ± 2.3 mm Hg respectively (age- and gender-adjusted Pearson's correlation coefficient r = -0.052; P = 0.001). In generalized estimating equation models adjusting for age, gender, and CCT, lower CH was significantly associated with longer AL (P < 0.001) and more myopic refractive error (P = 0.001). CONCLUSIONS: CH measurement is practical in young children because this is when myopia undergoes its most rapid progression. Prospective follow-up of this cohort at high risk for myopia is under way to determine whether low CH is predictive, or a consequence, of long AL.

Determinants of postoperative corneal edema and impact on goldmann intraocular pressure.

PURPOSE: Recent studies report that increased corneal edema because of contact lens wear under closed lids is associated with elevated Goldmann intraocular pressure (GAT IOP). We sought to assess whether the impact of postoperative corneal edema on GAT IOP would be similar and to determine the differential effect of different amounts of edema. METHODS: The setting is a tertiary level cataract clinic in Shantou, China. Pre- and postoperative (day 1) GAT IOP, central corneal thickness (CCT), corneal hysteresis, corneal resistance factor, and radius of corneal curvature were measured for consecutive patients undergoing phacoemulsification surgery by 2 experienced surgeons. Corneal edema was calculated as the percentage increase in CCT. RESULTS: Among 136 subjects (mean age, 62.5 ± 15.4 years; 53.7% women), the mean increase in CCT was 10.3% postoperatively. Greater corneal edema was associated with lower GAT IOP in unadjusted analyses (P < 0.03) and in linear regression models (P < 0.01). In the model, higher corneal resistance factor (P < 0.001), lower corneal hysteresis (P < 0.001), and steeper radius of corneal curvature (P < 0.001) were associated with higher GAT IOP. Among subjects with edema < the median, edema was associated with lower GAT IOP (P = 0.004), whereas among those with edema ≥ the median, edema was not associated with GAT IOP. An increase in CCT of 7% was associated with an 8 mm Hg underestimation of GAT IOP in our models. CONCLUSIONS: The effect of postoperative edema on GAT IOP seems to be the opposite of contact lens-induced edema. The magnitude of the effect is potentially relevant to patient management.

Intraocular pressure, central corneal thickness, and glaucoma in chinese adults: the liwan eye study.

PURPOSE: To describe the distribution of central corneal thickness (CCT), intraocular pressure (IOP), and their determinants and association with glaucoma in Chinese adults.DESIGN: Population-based cross-sectional study.METHODS: Chinese adults aged 50 years and older were identified using cluster random sampling in Liwan District, Guangzhou. CCT (both optical [OCCT] and ultrasound [UCCT]), intraocular pressure (by Tonopen, IOP), refractive error (by autorefractor, RE), radius of corneal curvature (RCC), axial length (AL), and body mass index (BMI) were measured, and history of hypertension and diabetes (DM) was collected by questionnaire. Right eye data were analyzed.RESULTS: The mean values of OCCT, UCCT, and IOP were 512 ± 29.0 μm, 542 ± 31.4 μm, and 15.2 ± 3.1 mm Hg, respectively. In multiple regression models, CCT declined with age (P < .001) and increased with greater RCC (P < .001) and DM (P = .037). IOP was positively associated with greater CCT (P < .001), BMI (P < .001), and hypertension (P < .001). All 25 persons with open-angle glaucoma had IOP <21 mm Hg. CCT did not differ significantly between persons with and without open- or closed-angle glaucoma. Among 65 persons with ocular hypertension (IOP >97.5th percentile), CCT (555 ± 29 μm) was significantly (P = .01) higher than for normal persons.CONCLUSIONS: The distributions of CCT and IOP in this study are similar to that for other Chinese populations, though IOP was lower than for European populations, possibly due to lower BMI and blood pressure. Glaucoma with IOP <21 mm Hg is common in this population. We found no association between glaucoma and CCT, though power (0.3) for this analysis was low.

Corneal hysteresis is correlated with reduction in axial length after trabeculectomy.

BACKGROUND: We sought to determine whether corneal biomechanical parameters are predictive of reduction in axial length after anti-metabolite trabeculectomy. METHODS: Chinese subjects undergoing trabeculectomy with mitomycin C by a single experienced surgeon underwent the following measurements: Corneal hysteresis (CH, Ocular Response Analyzer, Reichert Ophthalmic Instruments), Goldmann intra-ocular pressure (IOP), central corneal thickness (CCT) and axial length (AL, IOLMaster, Carl Zeiss Meditec, Dublin, CA) were measured pre-operatively, and AL, CH and IOP were measured 1 day and 1 week post-operatively. RESULTS: Mean age of 31 subjects was 52.0 ± 15.2 years, and 15 (48.4%) were female. The mean pre-operative IOP of 21.4 ± 9.3 mmHg was reduced to 8.2 ± 4.6 mmHg 1 day and 11.0 ± 4.4 mmHg 1 week post-operatively (p < 0.001). AL declined from 22.99 ± 0.90 to 22.76 ± 0.87 mm at 1 day and 22.74 ± 0.9 mm at 1 week; 30/31 (%) eyes had a decline in AL (p < 0.001, sign test). In multivariate linear regression models including post-operative data from 1 day and 1 week, greater decline in Goldmann IOP (p < 0.0001, greater pre-op axial length (p < 0.001) and lower pre-operative CH (p = 0.03), were all associated with greater decline in post-operative axial length. CONCLUSIONS: Eyes with lesser ability of the ocular coat to absorb energy (lower CH) had significantly greater decrease in axial length after trabeculectomy-induced IOP-lowering.

DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer

BACKGROUND: Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.

METHODS: We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day. The primary end point was the response rate, defined either as an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1, or as a reduction of at least 50% in the prostate-specific antigen level or a confirmed reduction in the circulating tumor-cell count from 5 or more cells per 7.5 ml of blood to less than 5 cells per 7.5 ml. Targeted next-generation sequencing, exome and transcriptome analysis, and digital polymerase-chain-reaction testing were performed on samples from mandated tumor biopsies.

RESULTS: Overall, 50 patients were enrolled; all had received prior treatment with docetaxel, 49 (98%) had received abiraterone or enzalutamide, and 29 (58%) had received cabazitaxel. Sixteen of 49 patients who could be evaluated had a response (33%; 95% confidence interval, 20 to 48), with 12 patients receiving the study treatment for more than 6 months. Next-generation sequencing identified homozygous deletions, deleterious mutations, or both in DNA-repair genes--including BRCA1/2, ATM, Fanconi's anemia genes, and CHEK2--in 16 of 49 patients who could be evaluated (33%). Of these 16 patients, 14 (88%) had a response to olaparib, including all 7 patients with BRCA2 loss (4 with biallelic somatic loss, and 3 with germline mutations) and 4 of 5 with ATM aberrations. The specificity of the biomarker suite was 94%. Anemia (in 10 of the 50 patients [20%]) and fatigue (in 6 [12%]) were the most common grade 3 or 4 adverse events, findings that are consistent with previous studies of olaparib.

CONCLUSIONS: Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate. (Funded by Cancer Research UK and others; ClinicalTrials.gov number, NCT01682772; Cancer Research UK number, CRUK/11/029.).

Retinal pigment epithelial cell multinucleation in the aging eye - a mechanism to repair damage and maintain homoeostasis

Retinal pigment epithelial (RPE) cells are central to retinal health and homoeostasis. Dysfunction or death of RPE cells underlies many age-related retinal degenerative disorders particularly age-related macular degeneration. During aging RPE cells decline in number, suggesting an age-dependent cell loss. RPE cells are considered to be postmitotic, and how they repair damage during aging remains poorly defined. We show that RPE cells increase in size and become multinucleate during aging in C57BL/6J mice. Multinucleation appeared not to be due to cell fusion, but to incomplete cell division, that is failure of cytokinesis. Interestingly, the phagocytic activity of multinucleate RPE cells was not different from that of mononuclear RPE cells. Furthermore, exposure of RPE cells in vitro to photoreceptor outer segment (POS), particularly oxidized POS, dose-dependently promoted multinucleation and suppressed cell proliferation. Both failure of cytokinesis and suppression of proliferation required contact with POS. Exposure to POS also induced reactive oxygen species and DNA oxidation in RPE cells. We propose that RPE cells have the potential to proliferate in vivo and to repair defects in the monolayer. We further propose that the conventionally accepted 'postmitotic' status of RPE cells is due to a modified form of contact inhibition mediated by POS and that RPE cells are released from this state when contact with POS is lost. This is seen in long-standing rhegmatogenous retinal detachment as overtly proliferating RPE cells (proliferative vitreoretinopathy) and more subtly as multinucleation during normal aging. Age-related oxidative stress may promote failure of cytokinesis and multinucleation in RPE cells.