Association of neovascular age-related macular degeneration with migraine.

Patients with early onset vascular pathology have been reported to manifest neovascular age-related macular degeneration (AMD). While the blood vessels involved in pathogenesis of migraine remains controversial, it is generally accepted that a major contributor is blood vessel pathology. This study aimed to examine the association between migraine and AMD using a nationwide population-based dataset. Retrospective claims data were collected from the Taiwan National Health Insurance Research Database. We identified 20,333 patients diagnosed with neovascular AMD (cases), and we selected 81,332 propensity score-matched controls from the remaining beneficiaries in Taiwan's National Health Insurance system. We used Chi-square tests to explore differences in the prevalence of migraine prior to the index date between cases and controls. We performed multiple logistic regressions to estimate the odds of prior migraine among neovascular AMD patients vs. controls after adjusting for age, sex, monthly income, geographic location, residential urbanization level, hyperlipidemia, diabetes, coronary heart disease, hypertension, and previous cataract surgery. A total of 5184 of sample patients (5.1%) had a migraine claim before the index date; 1215 (6.1%) among cases and 3969 (4.9%) among controls (p < 0.001), with an unadjusted OR of 1.239 (95% CI 1.160~1.324, p < 0.001) for prior migraine among cases relative to controls. Furthermore, the adjusted OR was 1.201 (95% CI 1.123~1.284; p < 0.001) for AMD cases relative to controls. The study offers population-based evidence that persons with migraine have 20% higher risk of subsequently being diagnosed with neovascular AMD.

The fungus-derived retinoprotectant theissenolactone C improves glaucoma-like injury mediated by MMP-9 inhibition.

BACKGROUND: Elevated intraocular pressure (IOP) is a major risk factor for glaucoma that has been found to induce matrix metalloproteinase-9 (MMP-9) activation and result in eventual retinal dysfunction. Proinflammatory cytokines such as monocyte chemoattractant protein-1 (MCP-1) and interleukin-1ß (IL-1ß) were also found to be involved in disease progression by mediating MMP-9 production. We previously reported that fungal derivative theissenolactone C (LC53) could exert ocular protective effects by suppressing neuroinflammation in experimental uveitis. PURPOSE: The aim of this study was to investigate the retinoprotective effects of natural compound LC53 on the high IOP-induced ischemia/reperfusion (I/R)-injury model of glaucoma and its cellular mechanisms. METHODS: A high IOP-induced I/R-injury model was manipulated by normal saline injection into the anterior chamber of the rat eye. MCP-1-stimulated monocytes and IL-1ß-activated primary astrocytes were used to investigate the cellular mechanisms of LC53. Retinal function was evaluated with the scotopic threshold response (STR) and combined rod-cone response by electroretinography (ERG). As a positive control, rats were treated with memantine. MMP-9 gelatinolysis, mRNA expression and protein expression were analyzed by gelatin zymography, RT-PCR, and Western Blot, respectively. The phosphorylation levels of MAPKs and NF-κB p65 were tested by Western Blot. Additionally, the levels of inflammatory MCP-1 and IL-1ß were determined by ELISA. RESULTS: The present study revealed that LC53 preserved the retina functional deficiency assessed by scotopic threshold response (STR) and combined rod-cone response of ERG after high IOP-induced I/R injury. These retinal protective effects of LC53 were positively correlated with inhibitory activities in I/R injury-elicited ocular MMP-9 activation and expression. The increased level of MCP-1 was not affected, and the enhanced IL-1ß production was partially reduced by LC53 in the retina after I/R injury. According to cellular studies, LC53 significantly and concentration-dependently abrogated MMP-9 activation and expression in MCP-1-stimulated THP-1 monocytes. We found the inhibitory activities of LC53 were through the ERK- and NF-κB-dependent pathways. In addition, LC53 dramatically suppressed IL-1ß-induced MMP-9 activation and expression in primary astrocytes. The phosphorylation of 65-kD protein (p65) of NF-κB was substantially blocked by LC53 in IL-1ß-stimulated primary astrocytes. CONCLUSION: LC53 exerted a retinal protective effect through NF-κB inhibition and was highly potent against MMP-9 activities after high IOP-induced I/R injury, suggesting that LC53 would be a promising drug lead for glaucoma or related medical conditions attributed to retinal ischemia.

Novel Protective Effects of Cistanche Tubulosa Extract Against Low-Luminance Blue Light-Induced Degenerative Retinopathy.

BACKGROUND/AIMS: Blue light-emitting diode light (BLL)-induced phototoxicity plays an important role in ocular diseases and causes retinal degeneration and apoptosis in human retinal pigment epithelial (RPE) cells. Cistanche tubulosa extract (CTE) is a traditional Chinese medicine with many beneficial protective properties; however, few studies have examined the ocular protective roles of CTE. In this study, we investigated the mechanisms underlying the effects of CTE on BLL-induced apoptosis in vitro and in vivo. METHODS: RPE cells were applied in the current in vitro study and cell viability was determined by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis-related protein expression was determined by western blot analysis and immunofluorescence staining. Brown Norway rats were used to examine exposure to commercially available BLL in vivo. Hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and western blot assays were used to examine retinal morphological deformation. RESULTS: CTE significantly inhibited hydrogen peroxide-, tert-butyl hydroperoxide-, sodium azide-, and BLL-induced RPE damage. Further, CTE reduced the expression of apoptotic markers such as cleaved caspase-3 and TUNEL staining after BLL exposure by inactivating apoptotic pathways, as shown via immunofluorescent staining. In addition, CTE inhibited the BLL-induced phosphorylation of c-Jun N-terminal kinase, extra signal-related kinases 1/2, and p38 in RPE cells. In vivo, the oral administration of CTE rescued 60-day periodic BLL exposure-induced decrements in retinal thickness and reduced the number of TUNEL-positive cells in the brown Norway rat model. CONCLUSION: CTE is a potential prophylactic agent against BLL-induced phototoxicity.

Theissenolactone C Exhibited Ocular Protection of Endotoxin-Induced Uveitis by Attenuating Ocular Inflammatory Responses and Glial Activation.

The aim of this study was to investigate the effects of a natural component, theissenolactone C (LC53), on the ocular inflammation of experimental endotoxin-induced uveitis (EIU) and its related mechanisms in microglia. Evaluation of the severity of anterior uveitis indicated that LC53 treatment significantly decreased iridal hyperemia and restored the clinical scores. Additionally, the deficient retina functions of electroretinography were improved by LC53. LC53 significantly reduced levels of tumor necrosis factor (TNF)-α, monocyte chemoattractant protein-1, protein leakage and activation of matrix metalloproteinases in the anterior section during EIU. Moreover, LC53 treatment decreased the oxidative stress as well as neuroinflammatory reactivities of GFAP and Iba-1 in the posterior section. Furthermore, LC53 decreased the phosphorylation of p65, expression of HSP90, Bax, and cleaved-caspase-3 in EIU. According to the microglia studies, LC53 significantly abrogated the productions of TNF-α, PGE2, NO and ROS, as well as inducible NO synthase and cyclooxygenase-2 expression in LPS-stimulated microglial BV2 cells. The microglial activation of IKKß, p65 phosphorylation and nuclear phosphorylated p65 translocation were strongly attenuated by LC53. On the other hand, LC53 exhibited the inhibitory effects on JNK and ERK MAPKs activation. Our findings indicated that LC53 exerted the ocular-protective effect through its inhibition on neuroinflammation, glial activation, and apoptosis in EIU, suggesting a therapeutic potential with down-regulation of the NF-κB signaling for uveitis and retinal inflammatory diseases.

Neovascular age-related macular degeneration is associated with cataract surgery.

PURPOSE: This retrospective cohort study examines the association between cataract surgery and neovascular age-related macular degeneration (AMD) during 5-year follow-up using population-based claims data. METHODS: We analysed data sourced from the Taiwan Longitudinal Health Insurance Database 2005. The study included 3465 patients who had undergone cataract operations and did not have a diagnosis of AMD before or on the surgery date (study group), and 10 395 age- and sex-matched comparison patients selected randomly from the remaining patients without an AMD diagnosis before the index date. We tracked the claims of each patient for a 5-year period to identify patients with a subsequent diagnosis of neovascular AMD. RESULTS: The incidence rate of neovascular AMD was 0.88 (95% confidence interval (CI): 0.66-1.14) per 1000 person-years among all sampled patients, 1.60 (95% CI: 1.04-2.36) among the cataract surgery patients and 0.64 (95% CI: 0.43-0.91) among comparison patients (p < 0.001). Stratified Cox proportional analysis showed that relative to the comparison cohort, the adjusted hazard ratio for neovascular AMD during 5-year follow-up was 2.68 (95% CI: 1.55-4.66) for patients who had undergone cataract operation. We censored those who died during follow-up period and adjusted for patients' monthly income, geographical location, urbanization level, diabetes, hypertension, cardiovascular disease and hyperlipidaemia. CONCLUSION: This study demonstrated epidemiological evidence of a link between cataract surgery and neovascular AMD during a 5-year follow-up period.

Anti-inflammatory properties of shikonin contribute to improved early-stage diabetic retinopathy.

Diabetic retinopathy (DR), a major microvascular complication of diabetes, leads to retinal vascular leakage, neuronal dysfunction, and apoptosis within the retina. In this study, we combined STZ with whole-body hypoxia (10% O2) for quicker induction of early-stage retinopathy in C57BL/6 mice. We also compared the effects of a high glucose condition combined with hypoxia (1% O2) to a low glucose condition by using retinal pigment epithelial (RPE) cells, which are a crucial component of the outer blood-retinal barrier and the damage is related to retinopathy. In the retina of DM/hypoxic C57BL/6 mice, abnormal a-wave and b-wave activity, yellowish-white spots, hyperfluorescence, and reduced retinal thickness were found using electroretinography (ERG), fundus photography (FP), fundus fluorescein angiography (FFA), and optical coherence tomography (OCT). Shikonin dose-dependently (0.5-50 mg/kg, per os) prevented DM/hypoxia-induced lesions. In eye tissue, administration of shikonin also attenuated DM/hypoxia-induced pre-apoptotic protein BAX expression as well as the production of inflammatory proteins cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). We also demonstrated that shikonin administration rescues high glucose/hypoxia (1% O2)-induced inflammation, decreased junction protein expression, and permeability in RPE cells. These results indicate that shikonin treatment may prevent the loss of vision associated with DR.

Incremental Healthcare Service Utilization for Open-angle Glaucoma: A Population-Based Study.

PURPOSE: To investigate differences in the utilization of healthcare services between subjects with open-angle glaucoma (OAG) and comparison subjects without OAG using Taiwan's National Health Insurance population-based database. PATIENTS AND METHODS: The study comprised 2204 subjects with OAG and 2204 sex-matched and age-matched subjects without OAG. We individually followed each subject for a 1-year period to evaluate their healthcare resource utilization. Outcome variables of the healthcare resource utilization were as follows: numbers of outpatient visits and inpatient days and the mean costs of outpatient and inpatient treatment. In addition, we divided healthcare resource utilization into ophthalmologic and nonophthalmologic services. RESULTS: As for the utilization of ophthalmologic services, OAG subjects had significantly more outpatient visits (7.4 vs. 1.3, P<0.001) and significantly higher outpatient costs (US$272 vs. US$39, P<0.001) than comparison subjects. For nonophthalmologic services, OAG subjects also had significantly more outpatient visits (29.4 vs. 21.8, P<0.001) and significantly higher outpatient costs (US$1263 vs. US$847, P<0.001) than comparison subjects. Furthermore, OAG subjects incurred significantly higher inpatient costs compared with comparison subjects (US$434 vs. US$234, P<0.001). For all healthcare services, OAG subjects had significantly more outpatient visits (36.8 vs. 23.1, P<0.001) and significantly higher outpatient (US$1535 vs. US$887, P<0.001) and total (US$2245 vs. US$1122, P<0.001) costs than comparison subjects. In other words, the total cost was about 2-fold greater for OAG subjects than comparison subjects. CONCLUSIONS: We concluded that subjects with OAG had significantly higher utilization of all healthcare services than comparison subjects.

Association of cataract with chronic rhinosinusitis: a population-based case-control study.

PURPOSE: To assess the association between cataract and chronic rhinosinusitis (CRS) using a population-based database. METHODS: The study sample for this case-control study was retrieved from Taiwan's Longitudinal Health Insurance Database 2000. The study included 3045 patients who had undergone cataract surgery as cases and 9135 subjects without cataract as controls. Conditional logistic regression was performed to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of having a prior diagnosis of CRS in cases versus controls. RESULTS: In the total study sample, the prevalence of prior CRS was 3.88%; 5.16% among cases and 3.45% among controls (p < 0.001). Conditional logistic regression suggested that the unadjusted OR for prior CRS among cases was 1.52 (95% CI 1.25-1.85, p < 0.001) compared to controls. After adjusting for monthly income, residential urbanization and geographic region, the OR for prior CRS among cases was 1.58 (95% CI 1.30-1.94, p < 0.001) compared to controls. Furthermore, the results consistently suggested that cases had higher adjusted ORs for prior CRS than controls across all age groups (40-59, 60-69, and >69 years). It is particularly noteworthy that younger groups demonstrated higher ORs for prior CRS among cases compared to controls. In particular, the adjusted OR for cases aged 40-50 years was 1.71 (95% CI 1.09∼2.66; p < 0.05) compared to controls. CONCLUSION: While the true relationship between CRS and cataract remains to be further investigated, the result of this present study demonstrated CRS may be associated with cataract.

Topiramate use and the risk of glaucoma development: a population-based follow-up study.

PURPOSE: To investigate the risk of glaucoma development after being prescribed topiramate. DESIGN: A retrospective, population-based cohort study using an administrative database. METHODS: The study group comprised 1956 patients who received their first prescription of topiramate between 2001 and 2007. The comparison cohort consisted of 15 648 randomly matched patients who never took topiramate. Each sampled patient was traced for a 1-year period from his or her index date to identify patients who subsequently received a diagnosis of glaucoma. RESULTS: Glaucoma was diagnosed in 0.36%, 0.05%, and 0.66% of the study cohort during the first month, second to third month, and fourth to twelfth month following the index date, respectively. For the comparison cohort, glaucoma was diagnosed in 0.04%, 0.11%, and 0.46% of subjects during the first month, second to third month, and fourth to twelfth month following the index date, respectively. After adjusting for potential confounding factors, patients prescribed topiramate were found to have a 7.41-fold (95% confidence interval [CI] = 2.45-22.46) greater risk of subsequently being diagnosed with glaucoma than the comparison cohort during the first month after the index date. However, this association became statistically nonsignificant during the second-to-third-month and fourth-to-twelfth-month periods following the index date between the 2 cohorts (adjusted hazard ratio, 0.56, 95% CI = 0.07-4.29; and 1.35, 95% CI = 0.74-2.47, respectively). CONCLUSIONS: Topiramate use in Taiwan was associated with a significantly increased risk of being diagnosed with glaucoma within the first month after receiving a prescription for the drug.

A one-year follow-up study on the incidence and risk of endophthalmitis after pyogenic liver abscess.

PURPOSE: Although endophthalmitis secondary to pyogenic liver abscess (PLA) is becoming a globally emerging infectious disease, population-based investigations evaluating the relationship between PLA and endogenous endophthalmitis remain scarce. This study aimed to investigate the incidence and risk of endogenous endophthalmitis in patients with PLA compared with unaffected individuals by using a nationwide, population-based dataset. DESIGN: Retrospective, cohort study. PARTICIPANTS AND CONTROLS: This study used data sourced from Taiwan's National Health Insurance Research Database. In total, 12 727 patients with PLA were included in the study group and 63 635 matched subjects were randomly extracted as a comparison group. METHODS: Stratified Cox proportional hazards regressions were performed to assess the effect of PLA on the hazard of developing endogenous endophthalmitis. MAIN OUTCOME MEASURES: The incidence and risk of endogenous endophthalmitis between the study group and comparison group. RESULTS: Of the total sample, 148 subjects (0.10%) were diagnosed with endophthalmitis during the 1-year follow-up period. Endophthalmitis was found in 106 patients (0.84%) with PLA and 42 comparison patients (0.07%). After adjusting for patient monthly income, geographic location, and urbanization level, those suffering from PLA were found to have a greater likelihood of developing endophthalmitis during the 1-year follow-up period than comparison patients (hazard ratio [HR], 12.83; 95% confidence interval, 8.94-18.41). Stratification did not reveal any large differences in the adjusted HRs for endophthalmitis between PLA patients suffering from diabetes and those in whom diabetes was absent. We further analyzed the etiology of cases with endogenous endophthalmitis in this investigation and found Klebsiella pneumonia to be the causative organism among 75.5% of the cases but only 33.4% of the comparison group. CONCLUSIONS: We found that the incidence and risk of developing endophthalmitis was significantly higher among patients with PLA compared with matched controls irrespective of diabetes status.

Role of taurine on acid secretion in the rat stomach.

BACKGROUND: Taurine has chemical structure similar to an inhibitory neurotransmitter, γ-aminobutyric acid (GABA). Previous studies on GABA in the stomach suggest GABAergic neuron is involved in acid secretion, but the effects of taurine are poor understood. METHODS: The effects of taurine on acid secretion, signal transduction, and localization of taurinergic neurons were determined in the rat stomach using everted whole stomach, RIA kit and immunohistochemical methods. RESULTS: We used antibodies against taurine-synthesizing enzyme, cysteine sulfuric acid decarboxylase (CSAD), and taurine. CSAD- and taurine-positive cells were found in the muscle and mucosal layers. Distributions of CSAD- and taurine-positive cells in both mucosal and muscle layers were heterogeneous in the stomach. Taurine at 10-9~10-4 M induced acid secretion, and the maximum secretion was at 10-5 M, 1.6-fold higher than the spontaneous secretion. Taurine-induced acid secretion was completely inhibited by bicuculline and atropine but not by cimetidine, proglumide, or strychnine. Atropine and tetrodotoxin (TTX) completely inhibited the acid secretion induced by low concentrations of taurine and partially inhibited induced by high concentrations. Verapamil, a calcium blocker agent, inhibited acid output elicited by taurine. We assumed all Ca2+ channels involved in the response to these secretagogues were equally affected by verapamil. Intracellular cAMP (adenosine 3', 5'-monophosphate) in the stomach significantly increased with taurine treatment in a dose-dependent manner. High correlation (r=0.859, p < 0.001) of taurine concentrations with cAMP was observed. CONCLUSIONS: Our results demonstrated for the first time in taurine-induced acid secretion due to increase intracellular calcium may act through the A type of GABA receptors, which are mainly located on cholinergic neurons though cAMP pathway and partially on nonneuronal cells in the rat stomach.

Increased risk of a cancer diagnosis after herpes zoster ophthalmicus: a nationwide population-based study.

PURPOSE: Herpes zoster has been associated with immune suppression, as has an increased risk of cancer. This population-based follow-up study aimed to investigate the risk of a subsequent cancer diagnosis after herpes zoster ophthalmicus (HZO). DESIGN: A retrospective cohort study. PARTICIPANTS AND CONTROLS: Retrospective claims data from the Taiwan National Health Insurance Research Database were analyzed. The study cohort comprised all patients with a diagnosis of HZO (International Classification of Diseases, 9th Revision, Clinical Modification code 053.2) in 2003 and 2004 (n=658). The comparison cohort consisted of randomly selected ambulatory care patients, 8 for every patient with HZO (n=5264) matched with the study group on age, gender, monthly income, and urbanization level of the patient's residence. METHODS: The Kaplan-Meier method was used to compute 1-year cancer-free survival rate. Stratified Cox proportional hazard regressions were carried out to compute the adjusted 1-year cancer-free survival rate after adjusting for potential confounding factors. MAIN OUTCOME MEASURES: Subsequent claims for all study and comparison patients were captured over a 1-year follow-up period from their index ambulatory care visit to identify whether the patient received a cancer diagnosis during the follow-up period. RESULTS: During 1-year follow-up, cancer was diagnosed in 4.86% of patients with HZO and 0.53% of patients in the comparison cohort. Patients with HZO had significantly lower 1-year cancer-free survival rates than the comparison cohort. After adjusting for patient age, gender, monthly income, and urbanization level, patients with HZO were found to have a 9.25-fold (95% confidence interval, 5.51-15.55) risk of a subsequent cancer diagnosis than the matched comparison cohort. No significant differences in cancer type were observed between the 2 cohorts. CONCLUSIONS: Herpes zoster ophthalmicus may be a marker of increased risk of being diagnosed with cancer in the following year. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Estimation accuracy of surgically induced astigmatism on the cornea when neglecting the posterior corneal surface measurement.

PURPOSE: To evaluate the accuracy of corneal surgically induced astigmatism (SIA) estimation when neglecting the posterior corneal surface measurement. METHODS: Fifty right eyes undergoing phacoemulsification were measured with a rotating Scheimpflug camera (Pentacam; Oculus Inc., Wetzlar, Germany) both before and after surgery. Clear corneal incisions with one suture were used in the phacoemulsification surgery. The keratometric corneal SIA (KSIA) was derived using the anterior corneal surface measurement and the keratometric index (1.3375) while neglecting the posterior corneal surface measurement. The Pentacam-derived total corneal SIA (PSIA) was derived by vergence tracing and polar value analysis [KP(135) and KP(180)] of the measurements on both corneal surfaces. RESULTS: The mean arithmetic estimation errors of the KSIA for the PSIA were 0.16 ± 0.32 (-0.52 to 1.14) D for the KP(135), and -0.02 ± 0.30 (-0.75 to 1.29) D for the KP(180). There was a significant difference between the KP(135) components of the KSIA and PSIA. Bivariate analysis revealed a statistically significant difference between the combined means of the KSIA and PSIA. Overall, 24% had either a KP(135) component of the KSIA that differed by > 0.50 D from that of the PSIA or a KP(180) component of the KSIA that differed by > 0.50 D from that of the PSIA. The blurring strength caused by neglecting the posterior corneal measurement was > 0.50 D in 24% of eyes. CONCLUSION: Neglecting the posterior corneal surface measurement may lead to significant deviation in the corneal SIA estimation after phacoemulsification in a proportion of eyes.

Accuracy of corneal astigmatism estimation by neglecting the posterior corneal surface measurement.

PURPOSE: To evaluate the accuracy of corneal astigmatism estimation by neglecting the posterior corneal surface measurement. DESIGN: Prospective, observational study. METHODS: The right eyes of 493 subjects were measured with a rotating Scheimpflug camera (Pentacam; Oculus, Wetzlar, Germany). The keratometric corneal astigmatism (KA) was obtained by using the anterior corneal surface measurement and the keratometric index (1.3375) while neglecting the posterior corneal surface measurement. The Pentacam-derived total corneal astigmatism (PA) was derived by doubled-angle vector analysis of the astigmatisms on both corneal surfaces. RESULTS: The mean arithmetic and absolute estimation errors of the KA magnitude for the PA magnitude were -0.06 +/- 0.28 diopters (D) (range, -0.59 to 0.91 D) and 0.24 +/- 0.16 D (range, 0 to 0.91 D), respectively. The mean arithmetic and absolute estimation errors of the KA angle for the PA angle were -0.6 degrees +/- 12.7 degrees (range, -69.9 degrees to 83.4 degrees) and 7.4 degrees +/- 10.3 degrees (range, 0 degrees to 83.4 degrees), respectively. Among all eyes, 142 eyes (28.8%) had either a KA magnitude that differed by > 0.50 D from the PA magnitude or a KA angle that differed by > 10 degrees from the PA angle. For the 282 eyes with a KA magnitude exceeding 1.0 D (that are candidates for intraoperative correction of a preexisting astigmatism during cataract surgery), 29 eyes (10.3%) had either a KA magnitude that differed by > 0.50 D from the PA magnitude or a KA angle that differed by > 10 degrees from the PA angle. CONCLUSIONS: Neglecting the posterior corneal surface measurement may lead to significant deviation in the corneal astigmatism estimation in a proportion of eyes.

Estimation of the effective lens position using a rotating Scheimpflug camera.

PURPOSE: To describe a no-history method of estimating the effective lens position (ELP) for double-K intraocular lens (IOL) power calculation in eyes that had previous refractive surgery. SETTING: Departments of Ophthalmology, Taipei Medical University Hospital and Taipei City Hospital, Taipei, Taiwan. METHODS: The corneal height (H(m)) and anterior chamber diameter (AG(m)) in 106 unoperated eyes were measured using a rotating Scheimpflug camera. The theoretical anterior corneal radius (R(rt)) was then derived from H(m) and AG(m) by regression and rearrangement of the Fyodorov equation. The ELP estimate was then calculated from R(rt). The performance of this ELP estimation method in double-K IOL power calculation and the performance of other methods were compared retrospectively in 11 eyes having cataract surgery that had previous refractive surgery. The refractive results 9 to 12 weeks after cataract surgery were selected for data analysis. RESULTS: The new ELP estimation method, combined with the BESSt formula or the Savini et al. method for estimating post refractive-surgery corneal power (K(post)) in the double-K SRK/T formula, provided the best IOL power prediction results. The mean arithmetic and absolute IOL prediction errors were -0.05+/-0.62 diopters (D) and 0.49+/-0.34 D, respectively, when combined with the BESSt formula and 0.03+/-0.73 D and 0.60+/-0.36 D, respectively, when combined with the Savini et al. method. With either combination, all 11 eyes were within+/-1.00 D of the refractive prediction error. CONCLUSION: This ELP estimation method may be helpful for IOL power calculation in post refractive-surgery eyes when historical data are unavailable.

Intraocular lens power calculation after automated lamellar keratoplasty for high myopia.

PURPOSE: To report intraocular lens (IOL) power calculation in 2 eyes that were highly undercorrected by previous myopic automated lamellar keratoplasty (ALK). METHODS: A 35-year-old man underwent bilateral myopic ALK, which caused high residual myopia (-9.0 -4.0 x 171 and -9.5 -4.5 x 74). The patient then underwent cataract surgery with IOL implantation for cataract development. The double-K clinical history method was utilized, and satisfactory IOL power prediction results were obtained. Two no-history IOL power calculation methods (Rosa correcting factor method and Ferrara theoretical variable refractive index method), which involved axial length-dependent modification of the keratometer-measured corneal radius, and 1 no-history IOL power calculation method (Shammas' method), which involved axial length-independent modification of the keratometer-measured corneal power, were tested on these 2 eyes. RESULTS: In both eyes, the double-K SRK-T clinical history method gave small IOL prediction errors (-0.66 and -0.81 D). The Shammas' no-history method gave a slightly higher IOL prediction error in the right eye (-1.67 D) and a small IOL prediction error in the left eye (-0.74 D). Unacceptable IOL power prediction errors would have resulted if Rosa's correcting factor method (-8.07 and -8.35 D) or Ferrara's theoretical variable refractive index method (-17.56 and -18.51 D) had been applied. When we utilized Rosa's method for the IOL power calculation by assuming that the previous ALK had fully corrected the refractive error, the predicted IOL powers were very close to the benchmark IOL powers (IOL power prediction errors: 1.16 and 0.37 D). When we utilized Ferrara's method with the same assumption, the IOL power prediction errors remained high (-6.32 and -7.16 D). CONCLUSIONS: For patients who have had previous myopic ALK (and whose eyes are highly undercorrected) and who require cataract surgery and for whom the pre-ALK history is available, the double-K method appears to yield excellent predictive results. However, if the pre-ALK history is not available, the Shammas' no-history method appears to yield better results than the Rosa's or the Ferrara's method. High undercorrection by the previous ALK might have been one of the major reasons why Rosa's method resulted in a high IOL prediction error in these 2 eyes. The cause for the marked IOL prediction error by Ferrara's method in this case, however, remains to be determined.

Validity of the keratometric index: evaluation by the Pentacam rotating Scheimpflug camera.

PURPOSE: To determine the keratometric index based on actual measurements of the anterior and posterior corneal surfaces using a rotating Scheimpflug camera (Pentacam, Oculus) and evaluate the accuracy of this keratometric index in estimating total and posterior corneal powers. SETTING: Departments of Ophthalmology, Taipei Medical University Hospital and Taipei City Hospital, Taipei, Taiwan. METHODS: The right eye of 221 subjects was measured with the Pentacam system. The radius of the best-fit sphere for the anterior corneal surface (rant) and posterior corneal surface (rpost), mean radius of simulated keratometry (rsimK), and central corneal thickness were obtained. The ratio of rant to rpost (AP ratio) and keratometric index were calculated in each eye. RESULTS: The means for rant, rpost, rsimK, and AP ratio were 7.75 mm +/- 0.28 (SD), 6.34 +/- 0.28 mm, 7.75 +/- 0.27 mm, and 1.223 +/- 0.034 mm, respectively. These parameters were normally distributed. The mean calculated keratometric index (Ncal) was 1.3281 +/- 0.0018. Using the keratometric indices of 1.3281 (Ncal), 1.3315 (Gullstrand schematic eye), and 1.3375 (conventional), the mean arithmetic and absolute estimation errors for the total corneal power were, 0.00 +/- 0.24 diopter (D) and 0.17 +/- 0.17 D, 0.43 +/- 0.23 D and 0.45 +/- 0.21 D, and 1.21 +/- 0.24 D and 1.21 +/- 0.24 D, respectively. The total corneal power was predicted to within +/-0.50 D of the actual value in 95.0%, 60.2%, and 0.9% of eyes, respectively. The mean arithmetic and absolute estimation errors for the posterior corneal power using an AP ratio of 1.223 (this study) or 1.132 (Gullstrand schematic eye) were 0.00 +/- 0.17 D and 0.13 +/- 0.12 D and 0.47 +/- 0.18 D and 0.47 +/- 0.17 D, respectively. The posterior corneal power was estimated to within +/-0.50 D of the actual value in 97.7% and 60.2% of eyes, respectively. CONCLUSION: Using the Pentacam-derived keratometric index improved the prediction accuracies of total and posterior corneal powers.

Ocular toxicity of intravitreal indocyanine green.

We report 6 cases of indocyanine green (ICG)-related ocular toxicity after intravitreal ICG usage. Five cases had preoperative diagnosis of macular hole, 1 case had preoperative rhegmatogenous retinal detachment complicated with proliferative vitreoretinopathy. All cases received vitrectomy, ICG-assisted internal limiting membrane (ILM) peeling and air-fluid exchange. All eyes had residual ICG left at the end of surgery. Patients were followed up with indirect ophthalmoscopy, visual acuity, color fundus photography, fluorescein angiography, and ocular coherence tomography. Circular foveal retinal pigment epithelium atrophy larger than the area of macular hole and surrounding cuff was noted in 4 of 5 cases with preoperative macular hole. The other eye with preoperative diagnosis of macular hole had shallow anterior chamber and low intraocular pressure lasting for 1 week postoperatively. Diffuse retinal pigment epithelial atrophy was noted in the eye with preoperative proliferative vitreoretinopathy. Four eyes demonstrated optic atrophy postoperatively. Ocular toxicity caused by ICG may present as pigment epithelial atrophy, which is characteristically larger than the previous area of macular hole and surrounding cuff. Disc atrophy, retinal toxicity, and ocular hypotony were also observed in some cases. To prevent toxicity, residual ICG and ICG-stained ILM must be removed as completely as possible.

Reduction of indocyanine green-associated photosensitizing toxicity in retinal pigment epithelium by sodium elimination.

OBJECTIVE: To determine if eliminating sodium affects indocyanine green (ICG) photosensitizing toxicity and uptake in cultured human retinal pigment epithelial (RPE) cells. METHODS: Cultured human RPE cells were exposed to ICG (2.5 mg/mL) in balanced salt solution and sodium-free balanced salt solution for 2 minutes. Afterwards, ICG was removed, and the cells were irradiated with a light beam (4 x 10(4) lux) for 40 minutes. Toxicity was monitored using light microscopy, calcein AM-ethidium homodimer 1 staining, trypan blue exclusion test, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium viability assay. Indocyanine green uptake was measured by optical absorption at 790 nm. RESULTS: Photoreactive changes occurred in RPE cells exposed to ICG and light. These changes included cell shrinkage, cell death, pyknotic nuclei, reduced viability, and reduced mitochondrial dehydrogenase activity. These changes were less severe when ICG was dissolved in sodium-free balanced salt solution. In addition, ICG uptake was reduced when the solvent was sodium-free balanced salt solution. CONCLUSION: Indocyanine green and intense light exposure in RPE cells caused photosensitizing toxicity that was reduced when sodium in the solvent was eliminated and replaced with other cations. CLINICAL RELEVANCE: Eliminating sodium from the solvent reduced ICG uptake into RPE and its associated photosensitizing toxicity. This reconstitution method of ICG may be helpful for safer intravitreal ICG use in macular hole surgery.

Cytotoxicity of indocyanine green on retinal pigment epithelium: implications for macular hole surgery.

OBJECTIVE: To evaluate the potential cytotoxic effects of indocyanine green (ICG) on cultured human retinal pigment epithelium (RPE) and the resultant implications for macular hole surgery. METHODS: Human RPE cells were exposed to ICG in concentrations from 0.001 to 5 mg/mL. The exposure duration ranged from 5 minutes to 3 hours. Light microscopy, MTS viability assay, and calcein AM-ethidium homodimer 1 staining were used to evaluate the cytotoxic effects of ICG. RESULTS: The RPE cells incubated with up to 5 mg/mL of ICG for 5 minutes or less exhibited no morphologic change and no significant decrease in dehydrogenase activity. When RPE cells were exposed to 5 mg/mL of ICG for 10 minutes, 1 mg/mL of ICG for 20 minutes, or 0.01 mg/mL of ICG for 3 hours, cell morphologic features were altered, mitochondrial dehydrogenase activity decreased, and some cells were necrotic. CONCLUSIONS: Indocyanine green caused cytotoxicity in cultured human RPE in a dose- and time-dependent manner. Cell death occurred by necrosis. CLINICAL RELEVANCE: Exposure of RPE cells to ICG concentrations up to 5 mg/mL for 5 minutes or less was not injurious; prolonged exposure to a low ICG concentration was toxic. Since ICG may be retained in the vitreous cavity for a lengthy period, thorough washout of ICG during macular hole surgery is required.