Aqueous humor immune factors and cytomegalovirus (CMV) levels in CMV retinitis through treatment - The CRIGSS study.

PURPOSE: This study aims to perform comprehensive longitudinal immune factor analysis of aqueous humor in relation to the aqueous CMV viral load and systemic CD4 counts during treatment of patients with co-infection of HIV and CMVR. METHODS: Aqueous humor samples were collected from 17 HIV-positive patients with CMVR scheduled to undergo weekly intravitreal ganciclovir therapy as part of the prospective CMV Retinitis Intravitreal Ganciclovir Singapore Study (CRIGSS) over the course of 1year. Full data across all the 4 time points was obtained and analyzed for CMV DNA viral load, 41 cytokine and chemokine factors using real-time PCR with the FlexMAP 3D (Luminex®) platform and assessed using the Milliplex Human Cytokine® kit. RESULTS: The following immune factors (Spearman correlation coefficient r value in parenthesis, p<0.05) showed strong correlation with CMV DNA load in the aqueous - MCP-1 (0.80, IFN-g (0.83), IP-10 (0.82), IL-8 (0.81), fractalkine (0.73), RANTES (0.68) - while the following showed moderate correlation - PDGF-AA (0.58), Flt-3L (0.59) and G-CSF (0.53). Only PDGF-AA revealed a statistically significant negative correlation with serum CD4 levels (r=-0.74). CONCLUSION: Immune factors that correlate with intraocular CMV DNA load are identified. They are indicative of a Th1 and monocyte-macrophage mediated response, and exhibit a decreasing trend longitudinally through the course of treatment. These factors may be an important new consideration in individualizing the treatment of patients with CMVR.

Accuracy of Toric Intraocular Lens Formulas With Measured Posterior Corneal Astigmatism of Different Orientations.

PURPOSE: To assess whether the use of measured posterior corneal astigmatism (PCA) values improves the prediction accuracy of toric intraocular lens power formulas, compared to predicted PCA values, when the orientation of the steep axis of PCA is non-vertical. DESIGN: Retrospective observational cohort study. METHODS: Four hundred eighteen eyes of 344 patients were included in the study. Prediction errors (PE) for postoperative refractive astigmatism at 4 weeks postoperatively were determined using vector analysis and compared for the following toric intraocular lens power formulas: Barrett Toric with predicted posterior corneal astigmatism (PPCA); Barrett Toric with measured posterior corneal astigmatism (MPCA); EVO Toric PPCA; EVO Toric MPCA; Holladay I with Abulafia-Koch regression. Subgroup analysis compared PEs for eyes with a vertically orientated steep axis of PCA (60-120°) to eyes with a non-vertically orientated steep axis of PCA. SETTING: Cathedral Eye Clinic, Belfast, United Kingdom and Tan Tock Seng Hospital, Singapore. RESULTS: Standard keratometry was with-the-rule in 48% of eyes, while the steep PCA axis was vertically orientated in 91% of eyes. For all eyes, EVO-PPCA had a smaller mean absolute error than Barrett-MPCA, Barrett-PPCA, and Abulafia-Koch (P < .01 for all). EVO-PPCA had the highest percentage of eyes within 0.50D of predicted postoperative astigmatism for eyes with vertical PCA (61%), while EVO-MPCA had the highest percentage for eyes with non-vertical PCA (54%). EVO-MPCA had the smallest centroid error for all eyes, and the subgroups (P < .01 for all). Eyes with non-vertical PCA had a lower percentage within 0.50D than eyes with vertical PCA when using PPCA (43% vs 61%, P = .034), but there was no significant difference between these groups when MPCA is used for eyes with non-vertical PCA (54% vs 61%, P = .40). CONCLUSIONS: When the steep axis of posterior corneal astigmatism is not vertically orientated, the use of measured posterior keratometry values improves prediction accuracy.

The Influence of Lens Position, Vault Prediction, and Posterior Cornea on Phakic Posterior Chamber Intraocular Lens Power.

BACKGROUND: Achieving precise refractive outcomes in phakic posterior chamber intraocular lens (pIOL) implantation is crucial for patient satisfaction. This study investigates factors affecting pIOL power calculations, focusing on myopic eyes, and evaluates the potential benefits of advanced predictive models. DESIGN: Retrospective, single-center, algorithm improvement study. METHODS: Various variations with different effective lens position (ELP) algorithms were analyzed. The algorithms included a fixed constant model, and a multiple linear regression model and were tested with and without incorporation of the posterior corneal curvature (Rcp). Furthermore, the impact of inserting the postoperative vault, the space between the pIOL and the crystalline lens, into the ELP algorithm was examined, and a simple vault prediction model was assessed. RESULTS: Integrating Rcp and the measured vault into pIOL calculations did not significantly improve accuracy. Transitioning from constant model approaches to ELP concepts based on linear regression models significantly improved pIOL power calculations. Linear regression models outperformed constant models, enhancing refractive outcomes for both ICL and IPCL pIOL platforms. CONCLUSIONS: This study underscores the utility of implementing ELP concepts based on linear regression models into pIOL power calculation. Linear regression based ELP models offered substantial advantages for achieving desired refractive outcomes, especially in lower to medium power pIOL models. For pIOL power calculations in both pIOL platforms we tested with preoperative measurements from a Scheimpflug device, we found improved results with the LION 1ICL formula and LION 1IPCL formula. Further research is needed to explore the applicability of these findings to a broader range of pIOL designs and measurement devices.

Differences Between Keratometry and Total Keratometry Measurements in a Large Dataset Obtained With a Modern Swept Source Optical Coherence Tomography Biometer.

PURPOSE: This study aimed to explore the concept of total keratometry (TK) by analyzing extensive international datasets representing diverse ethnic backgrounds. The primary objective was to quantify the disparities between traditional keratometry (K) and TK values in normal eyes and assess their impact on intraocular lens (IOL) power calculations using various formulas. DESIGN: Retrospective multicenter intra-instrument reliability analysis. METHODS: The study involved the analysis of biometry data collected from ten international centers across Europe, the United States, and Asia. Corneal power was expressed as equivalent power and astigmatic vector components for both K and TK values. The study assessed the influence of these differences on IOL power calculations using different formulas. The results were analyzed and plotted using Bland-Altman and double angle plots. RESULTS: The study encompassed a total of 116,982 measurements from 57,862 right eyes and 59,120 left eyes. The analysis revealed a high level of agreement between K and TK values, with 93.98% of eyes exhibiting an absolute difference of 0.25 D or less. Astigmatism vector differences exceeding 0.25 D and 0.50 D were observed in 39.43% and 1.08% of eyes, respectively. CONCLUSIONS: This large-scale study underscores the similarity between mean K and TK values in healthy eyes, with rare clinical implications for IOL power calculation. Noteworthy differences were observed in astigmatism values between K and TK. Future investigations should delve into the practicality of TK values for astigmatism correction and their implications for surgical outcomes.

Cytokine analysis of aqueous humor in HIV patients with cytomegalovirus retinitis.

PURPOSE: Cytomegalovirus retinitis (CMVR) is the most common opportunistic ocular infection in patients with AIDS. Comprehensive analysis of aqueous humor for immunologic factors has yet to be performed in patients with CMVR. This study aims to perform comprehensive immune factor analysis of aqueous humor in CMVR patients to determine the presence of any characteristic immunological profile in the aqueous humor. METHODS: Comparative prospective analysis of aqueous humor was performed across three groups: (1) AIDS patients with CMVR (CMVR group) (n=20), (2) HIV-positive patients without CMVR (HIV group) (n=6) and (3) patients undergoing cataract surgery with no underlying ocular infection or inflammation (control group) (n=11). At least 100µl of aqueous humor was drawn from all subjects and fractionated prior to analysis for 41 cytokines, chemokines and growth factors with the FlexMAP 3D (Luminex®) platform using the Milliplex Human Cytokine® kit. RESULTS: Three distinct immunologic signatures were observed in the aqueous humor of the three groups. Statistically significant differences (p<0.05) were observed across the three groups with the HIV group having lower levels and CMVR group having raised levels for the following factors: IP-10, fractalkine, PDGF-AA, G-CSF, Flt-3L and MCP-1. CONCLUSION: Aqueous humor though clinically quiescent in CMVR revealed a unique immunologic signature consistent with a combined Th-1 and monocyte-macrophage mediated response. Subsequent longitudinal analysis of aqueous cytokine levels of CMVR through the course of treatment would allow better understanding of the immunopathogenetic mechanisms of CMVR. This may also be used to better prognosticate the disease, predict complications and allow better assessment of treatment response and individualization of treatment in the future.

Accuracy of intraocular lens formulas using total keratometry in eyes with previous myopic laser refractive surgery.

OBJECTIVES: This comparative study aimed to determine if total keratometry (TK) from IOLMaster 700 could be applied to conventional formulas to perform IOL power calculation in eyes with previous myopic laser refractive surgery, and to evaluate their accuracy with known post-laser refractive surgery formulas. METHODS: Sixty-four eyes of 49 patients with previous myopic laser refractive surgery were evaluated 1 month after cataract surgery. A comparison of the prediction error was made between no clinical history post-laser refractive surgery formulas (Barrett True-K, Haigis-L, Shammas-PL) and conventional formulas (EVO, Haigis, Hoffer Q, Holladay I, and SRK/T) using TK values obtained with the optical biometer IOLMaster 700 (Carl Zeiss Meditec), as well as Barrett True-K with TK. RESULTS: The mean prediction error was statistically different from zero for Barrett True-K, Barrett True-K with TK, Haigis-L, Shammas-PL, and Holladay I with TK. The mean absolute error (MAE) was 0.424, 0.671, 0.638, 0.439, 0.408, 0.424, 0.479, 0.647, and 0.524, and median absolute error (MedAE) was 0.388, 0.586, 0.605, 0.298, 0.294, 0.324, 0.333, 0.438, and 0.377 for Barrett True-K, Haigis-L, Shammas-PL, Barrett True-K TK, EVO with TK, Haigis with TK, Hoffer Q with TK, Holladay I with TK, and SRK/T with TK, respectively. EVO TK followed by Barrett True-K TK and Haigis TK achieved the highest percentages of patients with absolute prediction error within 0.50 and 1.00 D (68.75%, 92.19%, and 64.06%, 92.19%, respectively) CONCLUSIONS: Formulas combined with TK achieve similar or better results compared to existing no-history post-myopic laser refractive surgery formulas.

VRF-G, a New Intraocular Lens Power Calculation Formula: A 13-Formulas Comparison Study.

PURPOSE: To compare the accuracy of a newly developed intraocular lens (IOL) power formula (VRF-G) with twelve existing formulas (Barret Universal II, EVO 2.0, Haigis, Hill-RBF 2.0, Hoffer Q, Holladay 1, Kane, Næeser 2, PEARL-DGS, SRK/T, T2 and VRF). METHODS: Retrospective case series including 828 patients having uncomplicated cataract surgery with the implantation of a single IOL model (SN60WF). Using optimised constants, refraction prediction error of each formula was calculated for each eye. Subgroup analysis was performed based on the axial length (short ≤22.0mm; medium >22.0mm to <26.0mm; long ≥26.0mm). Main outcomes included mean prediction error (ME) mean (MAE) and median absolute error (MedAE), in diopters (D), and the percentage of eyes within ±0.25D, ±0.50D, ±0.75D and ±1.00D. RESULTS: Formulas absolute errors were statistically different among them (p<0.001), with Kane having the lowest MAE of all formulas, followed by EVO 2.0 and VRF-G, which had the lowest MedAE. The Kane formula had the highest percentage of eyes within ±0.25D (47.0%) and ±1.00D (97.7%) and the VRF-G formula had the highest percentage of eyes within ±0.50D (79.5%). For all AL subgroups, Kane, EVO 2.0 and VRF-G formulas had the most accurate performances (lowest MAE). CONCLUSION: New generation formulas may help us in achieving better refractive results, lowering the variance in accuracy in extreme eyes - Kane, EVO 2.0 and VRF-G formulas are promising candidates to fulfil that goal.

Evaluation of the Accuracy of Two Marking Methods and the Novel toriCAM Application for Toric Intraocular Lens Alignment.

PURPOSE: To compare the accuracy of two common reference marking methods for toric intraocular lens alignment before and after using the novel toriCAM application. METHODS: In this prospective, randomized study, 22 participants were randomly allocated to two groups, either freehand or slit-lamp-assisted marking. Corneal markings at 0° and 180° were made using either method. The toriCAM application on a smartphone was then used to assess the rotational alignment of these markings and compared to the actual alignment as measured by the Zaldivar calipers on the iTrace Topographer (Tracey Technologies, Houston, TX) as a reference. The errors in marking with and without using the application were analyzed for all patients in each cohort and determined for each marking method. RESULTS: Twenty eyes of 11 patients were marked using the freehand method and 20 eyes of the other 11 patients were marked using the slit-lamp method. The mean absolute error of all markings before toriCAM adjustment was 3.18° ± 2.22°. This was significantly reduced to 1.28° ± 1.34° after using the application (P < .001). This improvement was also noted separately in the freehand and slit-lamp groups. Comparison of the freehand and slit-lamp methods did not show any statistically significant difference in accuracy at both time points. CONCLUSIONS: The novel toriCAM application is able to significantly improve the accuracy of reference marking for both freehand and slit-lamp methods. [J Refract Surg. 2018;34(3):150-155.].

Immune recovery uveitis in HIV patients with cytomegalovirus retinitis in the era of HAART therapy-a 5-year study from Singapore.

BACKGROUND: The aim of this study is to analyse the clinical features of HIV patients with cytomegalovirus retinitis (CMVR) developing immune recovery uveitis (IRU) while on highly active antiretroviral therapy (HAART) and to identify the risk factors, visual outcomes and complications of IRU. RESULTS: Majority (n = 26, 86.7 %) of patients were male, with 76.7 % (n = 23) of patients having bilateral disease. Twenty-seven eyes (50.9 %) had both anterior uveitis and vitritis. The median CD4 at IRU was 210 cells/µL (IQR 140-279), with 86.7 % having CD4 >100 cells/µL. The median duration from initiation of HAART to IRU was significantly different between those <50 years old (median 763 days, IQR 174-1872 days) and those ≥50 years old (median 161 days, IQR 84.5-278 days). Fourteen eyes (26.4 %) had loss of one or more Snellen lines visual acuity at 6 months while the rest maintained or improved vision. Complications developed in 21 eyes, with cataract (66.7 %), glaucoma and ocular hypertension (33.3 %) being the most common. The risk of complications was associated with the absolute difference in CD4 counts at IRU and at HAART commencement (p = 0.041). Age was also negatively associated with the duration from HAART to IRU (p = 0.005, Spearman's rho coefficient = -0.503). CONCLUSIONS: It is common to have both anterior uveitis and vitritis in IRU. There was a positive association between the increase in CD4 from HIV to IRU diagnoses and the risk of developing complications. Younger patients appeared to develop IRU later than older patients after HAART, suggesting that long-term follow-ups are essential for these patients.

Dataset of aqueous humor cytokine profile in HIV patients with Cytomegalovirus (CMV) retinitis.

The data shows the aqueous humor cytokine profiling results acquired in a small cohort of 17 HIV patients clinically diagnosed with Cytomegalovirus retinitis using the FlexMAP 3D (Luminex®) platform using the Milliplex Human Cytokine® kit. Aqueous humor samples were collected from these patients at different time points (pre-treatment and at 4-weekly intervals through the 12-week course of intravitreal ganciclovir treatment) and 41 cytokine levels were analyzed at each time point. CMV DNA viral load was assessed in 8 patients at different time points throughout the course of ganciclovir treatment. The data described herein is related to the research article entitled "Aqueous humor immune factors and cytomegalovirus (CMV) levels in CMV retinitis through treatment - The CRIGSS study" (Iyer et al., 2016) [1]. Cytokine levels against the different time points which indicate the response to the given treatment and against the CMV viral load were analyzed.

TNF-857T, a genetic risk marker for acute anterior uveitis.

PURPOSE: To determine the association between 17 single nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha, lymphotoxin-alpha, and the TNF-receptors genes (TNF, LTA, and TNFRSF1A and -B) and idiopathic acute anterior uveitis (IAU) and to investigate their association with HLA-B27 and/or the development of visually significant complications. METHODS: Ninety-eight white patients in the United Kingdom were identified (by SL) from the uveitis clinics of Moorfields Eye Hospital (London, UK). Sequence-specific primers with 3' end mismatches were used to identify the presence of specific allelic variants by PCR amplification. RESULTS: There was a significant increase in the frequency of the TNF-857T allele in patients with IAU when compared with control subjects (15.3% vs. 7.3%, P = 0.0006). The frequency of haplotype 4, containing the T allele at nucleotide position -857, was also significantly increased in patients with IAU compared with control subjects (15.4% vs. 7.1%, P = 0.0003, OR 2.4, 95% confidence interval 1.4-4.0). In subgroup analysis, there were significant differences in the frequencies of the uncommon TNFRSF1A-201T and TNFRSF1A-1135T alleles between HLA-B27(+) patients with inflammation-related complications and those without complications (80.0% vs. 33.6%, P = 0.006; 80.0% vs. 36.6%, P = 0.01, respectively). CONCLUSIONS: A significant difference in the frequency of TNF-857T allele was found in patients with IAU. There was a trend toward the development of inflammation-related complications in HLA-B27(+) patients with IAU who were carriers of TNFRSF1A-201T or TNFRSF1A-1135T alleles. Genetic variations in these proinflammatory mediators and their receptors appear to influence the susceptibility and severity of the inflammatory response within the eyes of patients during the development of IAU.

A prospective case-control study to investigate retinal microvascular changes in acute dengue infection.

Dengue infection can affect the microcirculation by direct viral infection or activation of inflammation. We aimed to determine whether measured retinal vascular parameters were associated with acute dengue infection. Patients with acute dengue were recruited from Communicable Diseases Center, Singapore and age-gender-ethnicity matched healthy controls were selected from a population-based study. Retinal photographs were taken on recruitment and convalescence. A spectrum of quantitative retinal microvascular parameters (retinal vascular caliber, fractal dimension, tortuosity and branching angle) was measured using a semi-automated computer-based program. (Singapore I Vessel Assessment, version 3.0). We included 62 dengue patients and 127 controls. Dengue cases were more likely to have wider retinal arteriolar and venular calibers (158.3 µm vs 144.3 µm, p < 0.001; 227.7 µm vs 212.8 µm, p < 0.001; respectively), higher arteriolar and venular fractal dimensions (1.271 vs 1.249, p = 0.002; 1.268 vs. 1.230, p < 0.001, respectively), higher arteriolar and venular tortuosity (0.730 vs 0.546 [x10(4)], p < 0.001; 0.849 vs 0.658 [x10(4)], p < 0.001; respectively), compared to controls. Resolution of acute dengue coincided with decrease in retinal vascular calibers and venular fractal dimension. Dengue patients have altered microvascular network in the retina; these changes may reflect pathophysiological processes in the immune system.

Causes of visual loss associated with uveitis in a singapore tertiary eye center.

PURPOSE: To identify the causes of visual loss associated with uveitis and its risk factors. METHODS: Review of 359 patients attending a uveitis service. RESULTS: Anterior uveitis (n = 229, 63.8%) was most common, followed by panuveitis (n = 55, 15.3%). There were 82 infective cases with 29.3% associated with tuberculosis. Visual loss occurred in 100 (27.9%) patients, of which 27 (7.5%) had severe visual loss. The main causes of visual loss were cataract (26%) and glaucoma (12%). Cystoid macular edema (14.8%) accounted for severe visual loss. Panuveitis was predictive for visual loss (p = 0.022, odds ratio (OR) 2.22) and severe visual loss (p = 0.01, OR 3.47). Posterior uveitis (p = 0.005, OR 5.01) and chronic uveitis (p = 0.008, OR 3.83) also showed higher risk for severe visual loss. CONCLUSION: With panuveitis being the second most common presentation, early specialist referral is essential in preventing visual loss.

Retinal vascular parameter variations in patients with human immunodeficiency virus.

PURPOSE: To compare the retinal vascular parameters in patients with human immunodeficiency virus (HIV) infection with normal controls, and to determine the relationship between retinal vascular parameters and HIV-related blood biomarkers (CD4(+) T-lymphocytes count, presence of HIV RNA). METHODS: Case-control study of eighty-five patients with HIV on follow-up at the Communicable Disease Center, Singapore, and 251 age-, sex-, and race-matched normal healthy controls (case: control matching ≈ 1:3) selected from the Singapore Epidemiology of Eye Disease program were included in this study. Standardized retinal photographs were taken from patients and controls. Trained technicians measured quantitative retinal vascular parameters (retinal vascular caliber, branching angle, tortuosity, and fractal dimension) with a semiautomated computer-based program following a standardized protocol. RESULTS: HIV-patients had more tortuous arterioles (0.77 × [10(4)] vs. 0.59 × [10(4)], P < 0.001) and venules (0.90 × [10(4)] vs. 0.74 × [10(4)], P < 0.001), compared with healthy normal subjects. Amongst the HIV-patients, increasing HIV viral loads were associated with decreased retinal arteriolar caliber (P trend = 0.009) and decreased arteriolar-venular ratio (P trend = 0.025). CONCLUSIONS: Our study showed that patients with HIV have significant variations in retinal vasculature. Retinal vascular imaging may offer further insight into the pathophysiology behind HIV-related vascular disease in future.

Spontaneous closure of traumatic macular hole.

Macular hole formation is a well-known complication following ocular trauma. Less commonly recognised is the spontaneous closure of such holes. A 27-year-old man presented with a history of blunt trauma to his left eye. Eye evaluation showed conjunctival laceration, diffuse retinal oedema and multiple retinal haemorrhages in that eye. A month later, he developed a full thickness macular hole. Two months later, there was spontaneous complete closure of the full-thickness macular hole in the left eye as confirmed on optical coherence tomography. Spontaneous closure of hole is not uncommon. Observation for a period of up to 12 months is a reasonable management option. Macular hole surgery for traumatic macular holes may be delayed in such cases.