Detecting Keratoconus in Adolescents with Anterior Segment Optical Coherence Tomography.

Purpose: Assessing the applicability of an algorithm developed for keratoconus detection in adolescents. This algorithm relies on optical coherence tomography (OCT) and incorporates features related to corneal pachymetric and epithelial thickness alterations. Methods: We retrospectively reviewed charts of patients under the age of 18 and divided them into four groups according to the Belin-Ambrosio display (Pentacam): normal, manifest, and subclinical keratoconus, as well as very asymmetric eye with normal topography and tomography (VAE-NTT). Corneal and epithelial thickness maps (Cirrus 5000 HD-OCT, Carl Zeiss Meditec, Germany) were evaluated by a human grader. In the first step, if at least one of four parameters (pachymetry minimum (pachy min), pachy minimum-median (min-med), pachy superonasal-inferotemporal (SN-IT), or epithelial (epi SN-IT)) exceeded its cut-off value, the eye was considered as suspect. In the second step, the combined presence of coincident thinning of total cornea and epithelium as well as concentric epithelial thinning lead to the diagnosis of keratoconus. Receiver operating characteristic (ROC) curves were generated to determine area under the curve (AUC), sensitivity, and specificity for the parameters. Results: The study involved 19 pediatric patients diagnosed with keratoconus, comprising 29 manifest keratoconic eyes, 3 eyes with subclinical keratoconus, and 5 VAE-NTT eyes. In addition, 22 eyes from 11 normal adolescents were included in the analysis. The AUC values of parameters in step 1 were 0.889 for pachy min, 0.997 for pachy min-med, 0.893 for pachy SN-IT, and 0.998 for epi SN-IT. When both steps were performed, this algorithm captured all manifest and subclinical pediatric keratoconic eyes. When all eyes of the keratoconus patients were combined, step 1 had 97.3% sensitivity and step 2 had 100% specificity. Conclusion: Using this OCT-based approach in adolescents yielded a high level of agreement with the current gold standard, tomography. Using them together, potentially also with other examinations may improve the diagnostic accuracy of KC in the pediatric population. Integration of this approach into the software of the device to facilitate automated evaluations is desired.

Risk Factors for Re-treatment After Keratorefractive Lenticule Extraction (KLEx) for Myopia and Myopic Astigmatism.

PURPOSE: To identify potential risk factors that increase the likelihood of re-treatment following keratorefractive lenticule extraction (KLEx) for myopia and myopic astigmatism. METHODS: This was a retrospective study of patients with myopia and myopic astigmatism who underwent KLEx using the VisuMax 500 laser (Carl Zeiss Meditec) between April 2015 and December 2020. Patients were assigned to one of two groups: the control group and the re-treatment group (if they had additional refractive surgery within 2 years of the primary treatment). The effect of different preoperative, intraoperative, and postoperative parameters on the re-treatment rate was analyzed. RESULTS: Overall 1,822 eyes of 938 patients were analyzed. In total, 2.96% of eyes (n = 54) underwent re-treatment. The re-treated patients were more likely to be women and have high myopia, high astigmatism, steep corneas, higher ocular residual astigmatism, and residual myopic and/or astigmatic refractive error. In contrast, no significant correlation was found between re-treatment rate and age, chord µ, type of astigmatism, and corneal thickness. CONCLUSIONS: Factors associated with higher rates of retreatment after KLEx included female gender, manifest refractive high myopia (> -5.00 diopters [D]), astigmatism (> 2.00 D), spherical equivalent (> 6.00 D), ocular residual astigmatism, steeper corneas, and postoperative residual myopic and astigmatic refractive errors. This study may help to preoperatively detect patients at risk for re-treatment, improve preoperative patient counseling, and optimize patient selection to reduce future re-treatment rates. [J Refract Surg. 2024;40(6):e362-e370.].

Protection against Oxidative Stress by Coenzyme Q10 in a Porcine Retinal Degeneration Model.

Oxidative stress plays an important role in neurodegenerative diseases, including glaucoma. Therefore, we analyzed if the antioxidant coenzyme Q10 (CoQ10), which is also commercially available, can prevent retinal degeneration induced by hydrogen peroxide (H2O2) in a porcine organ culture model. Retinal explants were cultivated for eight days, and H2O2 (500 µM, 3 h) induced the oxidative damage. CoQ10 therapy was applied (700 µM, 48 h). Retinal ganglion cells (RGCs) and microglia were examined immunohistologically in all groups (control, H2O2, H2O2 + CoQ10). Cellular, oxidative, and inflammatory genes were quantified via RT-qPCR. Strong RGC loss was observed with H2O2 (p ≤ 0.001). CoQ10 elicited RGC protection compared to the damaged group at a histological (p ≤ 0.001) and mRNA level. We detected more microglia cells with H2O2, but CoQ10 reduced this effect (p = 0.004). Cellular protection genes (NRF2) against oxidative stress were stimulated by CoQ10 (p ≤ 0.001). Furthermore, mitochondrial oxidative stress (SOD2) increased through H2O2 (p = 0.038), and CoQ10 reduced it to control level. Our novel results indicate neuroprotection via CoQ10 in porcine retina organ cultures. In particular, CoQ10 appears to protect RGCs by potentially inhibiting apoptosis-related pathways, activating intracellular protection and reducing mitochondrial stress.

Long-Term Astigmatism after Intraocular Pressure Sensor Implantation and Nonpenetrating Glaucoma Surgery - EYEMATE-SC Trial.

PURPOSE: To investigate the long-term astigmatism after combined non-penetrating glaucoma surgery (NPGS) and implantation of the first miniaturized suprachoroidal intraocular pressure (IOP) sensor EYEMATE-SC. SETTING: The study was conducted in five medical centers in two different countries. DESIGN: Retrospective multicenter clinical study. METHODS: Astigmatism of patients instrumented with the EYEMATE-SC IOP sensor was assessed over a follow-up period of three years. Refraction and corrected distance visual acuity (CDVA) were obtained preoperatively, after 6 months, 1, 2, and 3 years. A canaloplasty-operated patient cohort served as control. Astigmatism was evaluated using 3-dimensional power vector analysis involving the spherical equivalent M, and the Jackson crossed cylinder projections J0 and J45. Exclusion criteria included neovascular and angle-closure glaucoma, myopia, axial length outside 22 to 26 mm, other ocular diseases, prior glaucoma surgery, other ocular surgery within 6 months (cataract surgery within 3 months) prior to NPGS, serious generalized conditions, and other active medical head/neck implants. RESULTS: Multivariate analysis indicated no changes in astigmatism along the observation period in both the EYEMATE-SC (n = 24) and the canaloplasty (n = 24) group (P > 0.05 or nonsignificant after Bonferroni correction). Astigmatism was unchanged between the EYEMATE-SC and the canaloplasty group at all time points (P > 0.05). CDVA didn't change along the observation period of three years in each of both groups (P > 0.05). CONCLUSIONS: Despite its suprachoroidal localization, the present study indicates that the miniaturized EYEMATE-SC IOP sensor doesn't negatively affect the long-term astigmatism after combined implantation with NPGS.

In a novel autoimmune and high-pressure glaucoma model a complex immune response is induced.

Background: The neurodegenerative processes leading to glaucoma are complex. In addition to elevated intraocular pressure (IOP), an involvement of immunological mechanisms is most likely. In the new multifactorial glaucoma model, a combination of high IOP and optic nerve antigen (ONA) immunization leads to an enhanced loss of retinal ganglion cells accompanied by a higher number of microglia/macrophages in the inner retina. Here, we aimed to evaluate the immune response in this new model, especially the complement activation and the number of T-cells, for the first time. Further, the microglia/macrophage response was examined in more detail. Methods: Six-week-old wildtype (WT+ONA) and ßB1-connective tissue growth factor high-pressure mice (CTGF+ONA) were immunized with 1 mg ONA. A wildtype control (WT) and a CTGF group (CTGF) received NaCl instead. Six weeks after immunization, retinae from all four groups were processed for immunohistology, RT-qPCR, and flow cytometry, while serum was used for microarray analyses. Results: We noticed elevated numbers of C1q+ cells (classical complement pathway) in CTGF and CTGF+ONA retinae as well as an upregulation of C1qa, C1qb, and C1qc mRNA levels in these groups. While the complement C3 was only increased in CTGF and CTGF+ONA retinae, enhanced numbers of the terminal membrane attack complex were noted in all three glaucoma groups. Flow cytometry and RT-qPCR analyses revealed an enhancement of different microglia/macrophages markers, including CD11b, especially in CTGF and CTGF+ONA retinae. Interestingly, increased retinal mRNA as well as serum levels of the tumor necrosis factor α were found throughout the different glaucoma groups. Lastly, more T-cells could be observed in the ganglion cell layer of the new CTGF+ONA model. Conclusion: These results emphasize an involvement of the complement system, microglia/macrophages, and T-cells in glaucomatous disease. Moreover, in the new multifactorial glaucoma model, increased IOP in combination with autoimmune processes seem to enforce an additional T-cell response, leading to a more persistent pathology. Hence, this new model mimics the pathomechanisms occurring in human glaucoma more accurately and could therefore be a helpful tool to find new therapeutic approaches for patients in the future.

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.

Glaucoma Animal Models beyond Chronic IOP Increase.

Glaucoma is a complex and multifactorial disease defined as the loss of retinal ganglion cells (RGCs) and their axons. Besides an elevated intraocular pressure (IOP), other mechanisms play a pivotal role in glaucoma onset and progression. For example, it is known that excitotoxicity, immunological alterations, ischemia, and oxidative stress contribute to the neurodegeneration in glaucoma disease. To study these effects and to discover novel therapeutic approaches, appropriate animal models are needed. In this review, we focus on various glaucoma animal models beyond an elevated IOP. We introduce genetically modified mice, e.g., the optineurin E50K knock-in or the glutamate aspartate transporter (GLAST)-deficient mouse. Excitotoxicity can be mimicked by injecting the glutamate analogue N-methyl-D-aspartate intravitreally, which leads to rapid RGC degeneration. To explore the contribution of the immune system, the experimental autoimmune glaucoma model can serve as a useful tool. Here, immunization with antigens led to glaucoma-like damage. The ischemic mechanism can be mimicked by inducing a high IOP for a certain amount of time in rodents, followed by reperfusion. Thereby, damage to the retina and the optic nerve occurs rapidly after ischemia/reperfusion. Lastly, we discuss the importance of optic nerve crush models as model systems for normal-tension glaucoma. In summary, various glaucoma models beyond IOP increase can be utilized.

Comparison of toric intraocular lens alignment between femtosecond laser-assisted capsular marking and digital marking.

PURPOSE: To compare the accuracy of toric intraocular lens (IOL) alignment between femtosecond laser-assisted capsular marking and digital marking. SETTING: Ruhr University Eye Clinic, Bochum, Germany. DESIGN: Prospective clinical trial. METHODS: In this study, 28 eyes of 23 patients, who underwent femtosecond laser-assisted cataract surgery with implantation of a toric IOL, were included. Intraoperatively, both femtosecond laser-assisted capsular marking and digital marking were applied simultaneously and compared in every case. The toric IOL was aligned to the capsular markings. Postoperatively, the axis of the capsular markings and toric IOL alignment was examined. Visual acuity and refractive outcomes were evaluated. RESULTS: Both alignment methods were performed without intraoperative complications in all cases. 25 eyes were included in the final analysis. Misalignment was significantly lower with femtosecond laser-assisted capsular marking than with digital marking (1.71 ± 1.25 degrees vs 2.64 ± 1.70 degrees, P = .016). Deviation from the target axis of the toric IOL was 1.62 ± 1.24 degrees 4 to 6 weeks postoperatively. Postoperative uncorrected distance visual acuity was 0.14 ± 0.13 logMAR, and residual astigmatism was 0.3 ± 0.23 diopter (D) with an astigmatism ≤0.5 D in 93% of eyes. CONCLUSIONS: Both methods showed excellent results for the alignment of toric IOLs. However, femtosecond laser-assisted capsular marking was significantly more precise than digital marking and showed good refractive results. In addition, capsular marking offers the possibility to avoid parallax error and evaluating postoperative IOL rotation.

Two-Year Performance and Safety Results of the MINIject Supraciliary Implant in Patients With Primary Open-Angle Glaucoma: Meta-Analysis of the STAR-I, II, III Trials.

PURPOSE: To evaluate the performance and safety of minimally invasive glaucoma surgery with a supraciliary drainage device (MINIject; iSTAR Medical, Wavre, Belgium) in primary open-angle glaucoma (POAG) as a stand-alone procedure. DESIGN: Meta-analysis. METHODS: At 11 sites in Colombia, France, Germany, India, Panama, and Spain, 82 patients were treated in 3 prospective, multicenter, interventional, nonrandomized trials (STAR-I, II, III). Data were pooled in a meta-analysis of up to 2 years of follow-up postimplantation. The main outcome measures were mean relative and absolute reduction in diurnal intraocular pressure (IOP) compared to baseline. Secondary outcomes included patients with IOP ≤18 mmHg, patients with IOP reduction ≥20%, number of IOP-lowering medications, adverse events, and endothelial cell density loss. RESULTS: At the 2-year follow-up (n = 66), mean IOP was reduced from 23.8 ± 3.3 mmHg at baseline to 14.4 ± 4.5 mmHg (-39.3%; P < 0.0001). An IOP reduction of ≥20% was achieved in 89.4% of patients, with 84.8% having an IOP ≤18 mmHg. IOP-lowering medications were reduced from a mean of 2.4 ± 1.1 to 1.4 ± 1.4 (P < 0.0001), with 37.9% of patients being medication-free at 2 years. Mean endothelial cell density loss at 2 years was 6.2 ± 9.1% compared to baseline and no patient had a loss >30%. CONCLUSIONS: This meta-analysis demonstrates the favorable safety and efficacy profile of a supraciliary device implanted in a stand-alone, ab-interno procedure in patients with mild-to-moderate POAG. The data demonstrate that MINIject is a safe and effective, bleb-free treatment option for patients requiring low target IOP up to 2 years.

Investigation of Inter- and Intra-Day Variability of Tear Fluid Regarding Flow Rate, Protein Concentration as well as Protein Composition.

Purpose: The purpose of this study was to present the determination of inter- and intra-day variations in tear flow rate, and tear fluid protein concentration, as well as protein composition regarding their impact for future biomarker studies. Methods: Tear fluid was collected noninvasively from 18 healthy subjects by performing Schirmer tests at 4 different time points repetitive in a period of 2 days. The tear flow rate on the Schirmer test strips was measured. Proteins were extracted from strips and quantified using amino acid analysis. Protein composition was analyzed by the strips data-independent (DIA) based mass spectrometry. To exclude any impairments to health, volunteers underwent a detailed neurological as well as an ophthalmological examination. Results: Whether tear fluid was collected from oculus sinister or oculus dexter did not affect the tear flow rate (P ≈ 0.63) or protein concentration (P ≈ 0.97) of individual subjects. Moreover, protein concentration was independent from the tear volume, so that a change in volume may only influence the total protein amount. When the examination days were compared, investigation of tear flow rate (P ≈ 0.001) and protein concentration (P ≈ 0.0003) indicated significant differences. Further, mass spectrometric analysis of tear fluid revealed 11 differentially regulated proteins when comparing both examination days. Conclusions: Our findings provide evidence of inter-day variation in tear flow rate, tear proteome concentration, and composition in healthy subjects, suggesting that inter-day variation needs to be taken into consideration in biomarker research of tear fluid. Identified proteins were assigned to functions in the immune response, oxidative and reducing processes, as well as mannose metabolism.

Changes of Subjective Symptoms and Tear Film Biomarkers Following Lenticule Extraction.

PURPOSE: To investigate the influence of lenticule extraction on subjective symptoms and objective biomarkers of dry eye and to clarify relationships between markers and find indicators for subjective symptoms after lenticule extraction. METHODS: Right eyes of myopic patients undergoing lenticule extraction surgery (n = 35) were examined preoperatively and 5 and 90 days postoperatively using established clinical dry eye examination methods (tear film break-up time [BUT], Schirmer test, lissamine green and fluorescein staining, and Ocular Surface Disease Index (OSDI) questionnaire). A patient subset was also examined after 1 year (n = 14). Tear samples were eluted from Schirmer strips and then measured with enzyme-linked immunosorbent assays (calcitonin gene-related peptide (CGRP), interleukin-1ß, IL-6, IL-8, matrix metallopeptidase 9 [MMP-9], nerve growth factor, and tumor necrosis factor-α). Postoperatively, unpreserved ofloxacin and dexamethasone eye drops were given (four times a day for 10 days). RESULTS: BUT decreased at days 5 (P = .023) and 90 (P = .025). Lissamine green staining increased at day 90 (P = .036). OSDI values increased at day 5 (total values, vision-related function, ocular symptoms, all P < .001, but not environmental triggers) and at day 90 (vision-related function, P = .017). A downregulation of CGRP (P = .006) and MMP-9 levels (P = .042) was observed on day 5 compared to day 90. CONCLUSIONS: Due to incongruity of patient symptoms, clinical signs, and tear protein changes, no predictive indicator was found, but some patients reported increased discomfort. Changes after lenticule extraction are not exclusively due to dry eye. [J Refract Surg. 2023;39(9):597-604.].

HSP27 induced glaucomatous damage in mice of young and advanced age.

Introduction: Age-related diseases such as glaucoma, a leading cause of blindness, are having an upward trend due to an aging society. In glaucoma, some patients display altered antibody profiles and increased antibody titers, for example against heat shock protein 27 (HSP27). An intravitreal injection of HSP27 leads to glaucoma-like damage in rats. We now aimed to investigate if aged mice are more prone to this damage than younger ones. Methods: We intravitreally injected HSP27 into young (1-2 months) and aged (7-8 months) mice to compare glaucomatous damage. Respective age-matched controls received PBS. Not injected eyes served as naive controls. Results: Optical coherence tomography 4 weeks after injection showed no changes in retinal thickness in all groups at both ages. Cell counts and RT-qPCR revealed a significant reduction in RGC numbers in HSP27 mice at both ages. Comparing aged and young HSP27 mice, no differences in Rbpms and Pou4f1 (RGCs) expression was detected, while the Tubb3 expression (neuronal cells) was significantly upregulated in aged HSP27 animals. Neither microglia/macrophages nor (resident) microglia counts revealed significant differences in HSP27 mice at both ages. Nevertheless, increased relative Iba1 and Tmem119 expression was detected in young and aged HSP27 mice. Aged HSP27 mice displayed a significantly lower Iba1 expression than young ones, whereas Cd68 levels were upregulated. A larger GFAP+ area and an upregulation of GFAP expression in HSP27 animals of both ages indicated a macrogliosis. Also, elevated Il1b and Nos2 expression levels were observed in young and aged HSP27 mice. However, only Il1b levels were upregulated when comparing 7-8 months to 1-2 months old animals. A larger HSP25+ area was seen in aged HSP27 animals, while Hspb2 expression levels were downregulated in both HSP27 groups. The aged HSP27 group displayed an upregulated Hspb2 expression compared to young mice. Furthermore, a higher optic nerve degeneration score was noted in young and aged HSP27 groups. Discussion: These findings indicate that an intravitreal injection of HSP27 led to RGC loss accompanied by inflammation. Age-dependent effects (7-8 months vs. 1-2 months) were not very prominent. The results suggest a potential role of extracellular HSP27 in the development of glaucoma.

Capsular phimosis with intraocular lens tilt and decentration.

A 34-year-old woman with quiescent bilateral intermediate uveitis maintained on once-daily dexamethasone 0.1% eyedrops, complicated by left cataract and glaucoma controlled with a single antiglaucoma medication, presented for cataract surgery. Her left corrected distance visual acuity (CDVA) was 20/40 because of a posterior subcapsular lens opacity. The anterior chamber angles appeared closed in all 4 quadrants on gonioscopy. Ultrasound biomicroscopy (UBM) confirmed the gonioscopy findings and, in addition, revealed a crystalline lens thickness of 5.53 mm, normal ciliary body structure, and multiple localized chorioretinal scars with membranes over the pars plana region. She underwent left phacoemulsification, goniosynechiolysis, and in-the-bag implantation of a single-piece monofocal hydrophobic acrylic intraocular lens (IOL). On the first postoperative day, she achieved pinhole vision of 20/70 (-6 diopters [D] myopia to balance with the fellow eye). There was mild anterior chamber cellular activity and flare, consistent with postoperative inflammation. Her intraocular pressure (IOP) was 16 mm Hg without antiglaucoma therapy. She was advised to continue the prednisolone acetate 1% eyedrops 6 times daily and to reduce it to 4 times daily after a week for the next 4 weeks. At 1 month, she was refracted to 20/40 N5, and the eye was quiescent. Optical coherence tomography showed that the macular was normal. The topical steroids were gradually tapered to the preoperative level. However, a month later, she returned complaining of deteriorating vision while using twice-daily steroid eyedrops. Her CDVA was 20/60. Slitlamp examination revealed anterior capsule fibrosis and capsular phimosis, resulting in partial obstruction of the visual axis and mild decentration of the IOL superior temporally (Figure 1JOURNAL/jcrs/04.03/02158034-202310000-00013/figure1/v/2023-09-28T161738Z/r/image-tiff). The anterior segment was quiescent. The pupil could only be dilated to 4.5 mm despite the absence of posterior synechiae. Fundus examination revealed a normal-looking quiescent posterior segment. Her IOP was 16 mm Hg. UBM showed a thickened anterior capsule, intact zonular fibers, and a posteriorly bowed and decentered IOL within the capsular bag (Figure 2JOURNAL/jcrs/04.03/02158034-202310000-00013/figure2/v/2023-09-28T161738Z/r/image-tiff). She was referred for further management. Discuss how you would manage this problem, explaining your decisions. How would you be able to avoid the same problem when operating on her fellow eye?

Etiology of Idiopathic Macular Holes in the Light of Estrogen Hormone.

The aim of this review was to identify a new potential explanation for the development of macular holes in relation to the female sex and to explain the possible underlying pathways. This approach was based on the evaluation of anatomical, physiological, and morphological analyses currently available in the literature. The findings showed that estrogen exerts a protective effect on the neuroretina and may influence Müller and cone cells. Both cell types are responsible for the building of the fovea structure. However, this protection may be lost due to the sudden decrease in estrogen levels during menopause. In conclusion, the fovea cones, through its sensitivity to estrogen and high energy consumption, may be very vulnerable to damage caused by a sudden changes in the concentration of estrogen in menopausal females. Such changes may result in cone degeneration, and thus a destroyed structure of the fovea, and may lead to the development of a hole in the fovea, as in the case of macular holes. This review revealed that under the decreasing influence of estrogen may cones play a key role with regard to the etiology of the development of macular holes. This aspect may be of strategic importance in prophylactic therapy for the prevention of the development of macular holes in premenopausal females or after ocular trauma.

Rotational Stability After Implantation of Two Different Phakic Toric Intraocular Lenses.

PURPOSE: To compare clinical outcomes and rotational stability of the toric implantable Collamer lens (TICL) and toric implantable phakic contact lens (TIPCL). METHODS: Charts were reviewed from January 2011 to January 2023 to identify all TICLs and TIPCLs implanted by a single surgeon. Implant size was generally chosen according to the manufacturer's recommendation, but 15 TIPCLs 0.25 mm larger than recommended to increase vaulting were included. RESULTS: Eighty-four TICLs and 98 TIPCLs were identified and yielded excellent refractive and visual results in eyes with high myopic astigmatism at the last follow-up visit. No case of acute glaucoma or cataract induction was observed. In total, 15 (8.2%) rotated lenses were recorded; 2 (2.4%) TICLs and 13 (13.3%) TIPCLs (P = .013). Eyes in both groups were similar in preoperative spherical equivalent, cylinder, white-to-white distance, anterior chamber depth (ACD), anterior chamber angle, and mean follow-up times (P = .925, .673, .822, .794, .358, and .873, respectively). Average TICL size was larger than TIPCL size (P < .001). Rotation of the lenses was positively correlated with cylinder and negatively correlated with ACD but not with vaulting (P = .001, r = 0.253; P = .011, r = -0.193; P = .488, r = -0.057; respectively). Vaulting was positively correlated with preoperative ACD (P ≤ .001, r = .329). In eyes with a rotated TIPCL, preoperative cylinder was higher and ACD was shallower than in eyes with a stable TIPCL (P = .001 and .007, respectively). Increasing the implant size had no significant effect on rotation rate (P = .685). CONCLUSIONS: Although both implants were safe and effective in highly myopic eyes, TICL rotated less frequently than TIPCL and required fewer secondary interventions. Rotation was correlated with preoperative cylinder and ACD but not lens vaulting. [J Refract Surg. 2023;39(7):463-472.].

Decision taking in corneal refractive surgery.

A 27-year-old woman who wants to get rid of contact lenses and spectacles was seen at our clinic. She had strabismus surgery as a child and was patched for the right eye but now shows mild nondisturbing exophoria. Infrequently, she likes to box in the sports school. Her corrected distance visual acuity at presentation in the right eye was 20/16 with -3.75 -0.75 × 50 and in the left eye 20/16 with -3.75 -1.25 × 142. Her cycloplegic refraction in the right eye was -3.75 -0.75 × 44 and in the left eye was -3.25 -1.25 × 147. The left eye is the dominant eye. The tear break-up time was 8 seconds in both eyes, and the Schirmer tear test was 7 to 10 mm in right and left eyes, respectively. Pupil sizes under mesopic conditions were 6.62 mm and 6.68 mm. The anterior chamber depth (ACD) (measured from the epithelium) in the right eye was 3.89 mm and in the left eye was 3.87 mm. The corneal thickness was 503 µm and 493 µm of the right and left eye, respectively. Corneal endothelial cell density was on average 2700 cells/mm2 for both eyes. Slitlamp biomicroscopy showed clear corneas and a normal flat iris configuration. Supplemental Figures 1 to 4 (available at http://links.lww.com/JRS/A818, http://links.lww.com/JRS/A819, http://links.lww.com/JRS/A820, and http://links.lww.com/JRS/A821) show the corneal topography and Belin-Ambrósio deviation (BAD) maps at presentation of the right eye and left eye, respectively. Would you consider this patient a candidate for corneal refractive surgery (eg, laser-assisted subepithelial keratectomy, laser in situ keratomileusis [LASIK], or small-incision lenticule extraction [SMILE] procedure)? Has your opinion changed given the recent opinion of the U.S. Food and Drug Administration (FDA) regarding LASIK?1 The patient herself is slightly favoring an implantation of a phakic intraocular lens (pIOL), as she prefers something reversible. Would you implant a pIOL, and which type of IOL, for this level of myopia? What is your diagnosis or are additional diagnostic methodologies needed to establish a diagnosis? What is your treatment advice for this patient? REFERENCES 1. U.S. Food and Drug Administration, HHS. Laser-assisted in situ keratomileusis (LASIK) lasers-patient labeling recommendations; draft guidance for industry and food and drug administration staff; availability. July 28, 2022, Federal Register; 87 FR 45334. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/laser-assisted-situ-keratomileusis-lasik-lasers-patient-labeling-recommendations Accessed January 25, 2023.

Increased Angiopoietin-1 and -2 levels in human vitreous are associated with proliferative diabetic retinopathy.

BACKGROUND: Diabetic retinopathy is a frequent complication of diabetes mellitus and a leading cause of blindness in adults. The objective of this study was to elucidate the diabetic retinopathy pathophysiology in more detail by comparing protein alterations in human vitreous of different diabetic retinopathy stages. METHODS: Vitreous samples were obtained from 116 patients undergoing pars plana vitrectomy. Quantitative immunoassays were performed of angiogenic factors (VEGF-A, PIGF, Angiopoietin-1, Angiopoietin-2, Galectin-1) as well as cytokines (IL-1ß, IL-8, IFN-γ, TNF-α, CCL3) in samples from control patients (patients who don't suffer from diabetes; n = 58) as well as diabetes mellitus patients without retinopathy (n = 25), non-proliferative diabetic retinopathy (n = 12), and proliferative diabetic retinopathy patients (n = 21). In addition, correlation analysis of protein levels in vitreous samples and fasting glucose values of these patients as well as correlation analyses of protein levels and VEGF-A were performed. RESULTS: We detected up-regulated levels of VEGF-A (p = 0.001), PIGF (p<0.001), Angiopoietin-1 (p = 0.005), Angiopoietin-2 (p<0.001), IL-1ß (p = 0.012), and IL-8 (p = 0.018) in proliferative diabetic retinopathy samples. Interestingly, we found a strong positive correlation between Angiopoietin-2 and VEGF-A levels as well as a positive correlation between Angiopoietin-1 and VEGF-A. CONCLUSION: This indicated that further angiogenic factors, besides VEGF, but also pro-inflammatory cytokines are involved in disease progression and development of proliferative diabetic retinopathy. In contrast, factors other than angiogenic factors seem to play a crucial role in non-proliferative diabetic retinopathy development. A detailed breakdown of the pathophysiology contributes to future detection and treatment of the disease.

Safety and performance of a suprachoroidal sensor for telemetric measurement of intraocular pressure in the EYEMATE-SC trial.

AIM: To investigate the safety and performance of a telemetric suprachoroidal intraocular pressure (IOP) sensor (EYEMATE-SC) and the accuracy of its IOP measurements in open angle glaucoma (OAG) patients undergoing simultaneous non-penetrating glaucoma surgery (NPGS). METHODS: Prospective, multicentre, open-label, single-arm, interventional clinical trial. Twenty-four eyes of 24 patients with OAG regularly scheduled for NPGS (canaloplasty or deep sclerectomy) were simultaneously implanted with an EYEMATE-SC sensor. Six-month follow-up on the sensor's safety and performance as well as on the level of agreement between the EYEMATE-SC measurements and IOP measurements with Goldmann applanation tonometry (GAT). RESULTS: The eyes underwent canaloplasty (n=15) or deep sclerectomy (n=9) and achieved successful implantation of the sensor. No device migration, dislocation or serious device-related complications occurred. A total of 367 comparisons were included in the IOP agreement analysis. The overall mean difference between GAT and EYEMATE-SC measurements was 1.31 mm Hg (lower limit of agreement (LoA) 7.55 mm Hg; upper LoA -4.92 mm Hg). The maximum difference of 2.5 mm Hg ±3.96 (LoA 0.30-2.29) was reached on day 10 and continuously improved to an agreement of -0.15 mm Hg ±2.28 (LoA -1.24 to 0.89) after 6 months. Accordingly, the percentage of eyes within an IOP difference of ±5 mm Hg improved from 78% (day 3) to 100% (6 months). CONCLUSIONS: After 6 months, the EYEMATE-SC sensor was safe and well tolerated, and allowed continual IOP monitoring. TRIAL REGISTRATION NUMBER: NCT03756662.

EYEMATE-SC Trial: Twelve-Month Safety, Performance, and Accuracy of a Suprachoroidal Sensor for Telemetric Measurement of Intraocular Pressure.

PURPOSE: Measuring and controlling intraocular pressure (IOP) provide the foundation for glaucoma treatment. Self-tonometry has been proposed as an alternative to measure IOP throughout the entire day better. The novel EYEMATE-SC sensor (Implandata) is implanted in the suprachoroidal space to enable contactless continual IOP monitoring. The aim of the present study was to investigate the 1-year safety, performance, and accuracy of the EYEMATE-SC in patients with primary open-angle glaucoma undergoing simultaneous nonpenetrating glaucoma surgery (NPGS). DESIGN: Prospective, multicenter, open-label, single-arm, interventional clinical trial. PARTICIPANTS: Twenty-four eyes of 24 patients with primary open-angle glaucoma who were due to undergo NPGS (canaloplasty or deep sclerectomy). METHODS: An EYEMATE-SC sensor was implanted during NPGS. Goldmann applanation tonometry (GAT) measurements were compared with the sensors' IOP measurements at all postoperative visits through 12 months. MAIN OUTCOME MEASURES: Device position and adverse events. RESULTS: Fifteen eyes underwent canaloplasty, and 9 underwent deep sclerectomy. Successful implantation of the sensor was achieved in all eyes with no reported intraoperative difficulties. Through the 12-month follow-up, no device migration, dislocation, or serious device-related complications were recorded. A total of 536 EYEMATE-SC measurements were pairwise included in the IOP agreement analysis. The overall mean difference between GAT and EYEMATE-SC measurements was 0.8 mmHg (95% confidence interval [CI] of the limits of agreement [LoA], -5.1 to 6.7 mmHg). The agreement gradually improved, and from 3 months after surgery until the end of the follow-up, the mean difference was -0.2 mmHg (95% CI of LoA, -4.6 to 4.2 mmHg) over a total of 264 EYEMATE-SC measurements, and 100% of measurements were within ±5 mmHg of GAT. CONCLUSIONS: The EYEMATE-SC sensor was safe and well tolerated through 12 months. Moreover, it allowed accurate, continuous IOP monitoring. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Heat Shock Protein Upregulation Supplemental to Complex mRNA Alterations in Autoimmune Glaucoma.

Glaucomatous optic neuropathy is a common cause for blindness. An elevated intraocular pressure is the main risk factor, but also a contribution of the immune system seems likely. In the experimental autoimmune glaucoma model used here, systemic immunization with an optic nerve homogenate antigen (ONA) leads to retinal ganglion cell (RGC) and optic nerve degeneration. We processed retinae for quantitative real-time PCR and immunohistology 28 days after immunization. Furthermore, we performed mRNA profiling in this model for the first time. We detected a significant RGC loss in the ONA retinae. This was accompanied by an upregulation of mRNA expression of genes belonging to the heat shock protein family. Furthermore, mRNA expression levels of the genes of the immune system, such as C1qa, C1qb, Il18, and Nfkb1, were upregulated in ONA animals. After laser microdissection, inner retinal layers were used for mRNA microarrays. Nine of these probes were significantly upregulated in ONA animals (p < 0.05), including Hba-a1 and Cxcl10, while fifteen probes were significantly downregulated in ONA animals (p < 0.05), such as Gdf15 and Wwox. Taken together, these findings provide further insights into the pivotal role of the immune response in glaucomatous optic neuropathy and could help to identify novel diagnostic or therapeutic strategies.