The large Hellenic Study of Uveitis: epidemiology, etiologic factors and classification.

PURPOSE: To analyse the demography, etiology, and classification of uveitis at a tertiary academic referral center. METHODS: An observational study was conducted on the archives of uveitic patients at the Ocular Inflammation Service of the Department of Ophthalmology at the University Hospital of Ioannina (Greece) from 1991 to 2020. This study aimed to investigate the epidemiological profile of patients, including their demographics and the main etiologic factors of uveitis. RESULTS: Out of 6191 cases with uveitis, 1925 were infectious, 4125 were non-infectious, and an overall of 141 masquerade syndromes were recorded. Among these cases, 5950 patients were adults, with a slight female predominance, while 241 were children (< 18 years old). Interestingly, 24.2% of cases (1500 patients) were associated with 4 specific microorganisms. Herpetic uveitis (HSV-1 and VZV/HZV) was the most common cause of infectious uveitis (14.87%), followed by toxoplasmosis (6.6%) and tuberculosis (2.74%). In 49.2% of non-infectious uveitis cases, no systematic correlation was found. The most frequent causes of non-infectious uveitis included sarcoidosis, white dot syndromes, ankylosing spondylitis, lens-induced uveitis, Adamantiades-Behçet disease, and idiopathic juvenile arthritis. Infectious uveitis was more common in the rural population, whereas non-infectious uveitis was more frequently recorded in the urban population CONCLUSIONS: Although our study was conducted on a predominantly white Caucasian population, it also reflects the effect of increasing immigration, improvements of diagnostic techniques, changes in referral patterns, and various actual changes in disease incidence.

The Large Hellenic Study of Uveitis: Diagnostic and Therapeutic Algorithms, Complications, and Final Outcome.

PURPOSE: The purpose of this study is to present the diagnostic and therapeutic algorithms, complications, and final outcome in the management of uveitic patients at a tertiary academic referral center. DESIGN: Observational study. METHODS: Analysis of the archives of 6191 uveitic patients at the Ocular Inflammation Service of the Department of Ophthalmology of the University Hospital of Ioannina in Greece from 1991 to 2020. RESULTS: During the 30 years of the study, the diagnostic ability climbed from 45.43% (1991-1995) to 73.4% (2016-2020). This improvement was linked to several factors including the increase in the number of diagnostic paracenteses for the analysis of intraocular fluids, the range and quality of laboratory blood tests, the multimodal ophthalmic imaging, the proper use of nonophthalmic imaging, and the multidisciplinary approach. The degree of uveitis-related complications was related to the severity and cause of inflammation, the recurrence rate, inappropriate treatment, and the prolonged or initially inactive inflammation. The 3 most common complications included cataract, macular edema, and glaucoma. Apart from the modern treatments and surgical techniques, the 3-month preoperative control of inflammation played a critical role in the surgical outcomes. The percentage of patients with a successful outcome increased from 72% (2001-2005) to 90.50% (2016-2020). The center's experience, prompt referral, patient's compliance, and regular follow-ups are associated with a better outcome. The analysis of the results allowed the development of diagnostic and therapeutic algorithms. CONCLUSIONS: Developing diagnostic and therapeutic algorithms allows for the efficient management of uveitis, leading to better visual outcome and therefore a better quality of life.

Optical coherence tomography biomarkers for visual acuity in patients with idiopathic epiretinal membrane.

PURPOSE: To investigate the correlation between outer and inner retina optical coherence tomography (OCT) biomarkers and visual acuity in patients with idiopathic epiretinal membrane (iERM) and identify which of them may be predictive of visual function. METHODS: A retrospective cross-sectional single-center study was conducted that included patients diagnosed with iERM. Spectral domain OCT images were obtained and assessed qualitatively and quantitatively. The association of OCT parameters with best corrected visual acuity was analyzed. RESULTS: Charts of 97 eyes of 97 patients were reviewed. Central foveal thickness, maximal retinal thickness (MRT), photoreceptor outer segment length, outer foveal thickness, ganglion cell-inner plexiform layer complex thickening, inner retinal thickness and inner retinal layer irregularity index were among the major outcome measures. OCT scans were also assessed for the presence of cotton ball sign, ellipsoid zone disruption, ectopic inner foveal layer, disorganization of retinal inner layers (DRIL), intraretinal fluid, subretinal fluid (SRF) and epimacular membrane rip. Univariate analysis showed statistically significant association between all the aforementioned parameters with worse vision, except for cotton ball sign and SRF. Multivariate analysis found that MRT and severe DRIL were strongly correlated with worse vision (p < 0.001). CONCLUSION: MRT and severe DRIL should be considered as negative prognostic factors for visual acuity.

A Critical Overview of the Biological Effects of Mitomycin C Application on the Cornea Following Refractive Surgery.

During the last 2 decades, modifying the shape of the cornea by means of laser photoablation has emerged as a successful and popular treatment option for refractive errors. Corneal surface ablation techniques such as photorefractive keratectomy (PRK) and laser-assisted subepithelial keratomileusis (LASEK) offer good refractive results while having a minimal impact on corneal biomechanical stability. Past limitations of these techniques included the long-term regression of refractive outcome and a vigorous healing response that reduced corneal clarity in some patients (giving rise to what is clinically described as "haze"). Mitomycin C (MMC) was introduced as a healing modulator and applied on the corneal surface after refractive surgery to address these drawbacks. This article critically reviews the available evidence on the biological effects, safety, and clinical benefits of the off-label use of MMC in corneal refractive surgery.

Retrobulbar hemodynamics and aqueous humor levels of endothelin-1 in exfoliation syndrome and exfoliation glaucoma.

BACKGROUND: Endothelin-1 (ET-1) is the most potent vasoconstrictor in the body. There are reports in the literature correlating plasma levels of ET-1 and its impact on retrobulbar hemodynamics. This study evaluates aqueous humor levels of ET-1 and retrobulbar hemodynamics in patients with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG). PATIENTS AND METHODS: Patients scheduled for cataract surgery were included. Patients were allocated to non-exfoliation non-glaucoma group (controls), XFG and XFS groups. Peak systolic velocity (PSV), end diastolic velocity, and resistivity index of the ophthalmic artery (OA), short posterior ciliary arteries, and central retinal artery (CRA) were determined preoperatively using color Doppler imaging. Aqueous humor samples obtained at the beginning of cataract surgery were analyzed with enzyme-linked immunosorbent assay. RESULTS: Sixty-nine participants of similar age were included (controls: n=24, XFG: n=22, XFS: n=23). Multiple regression analysis showed that ET-1, OA-PSV, OA-resistivity index, CRA-PSV, and CRA-end diastolic velocity were influenced by group but not by sex or age. ET-1 for the XFG group (15.93±2.8 pg/mL) was significantly higher than for the XFS (8.92±2.7 pg/mL) and control (8.44±2.6 pg/mL) groups. The difference in ET-1 titers between the control and XFS groups was not statistically significant. All four hemodynamic parameters affected by group status significantly correlated with ET-1 levels in eyes with XFS. In eyes with XFG, two of the four hemodynamic parameters significantly correlated with ET-1 levels. In control eyes, no correlation between ET-1 and hemodynamic parameters affected by group status was detected. CONCLUSION: ET-1 aqueous levels in eyes with XFG were significantly higher than those of age-matched controls. Reduced blood flow and increased vascular resistivity were detected in the OA and the CRA in eyes with XFG/XFS. ET-1 levels in eyes with XFG/XFS exhibit a significant correlation with hemodynamic parameters that indicate reduced perfusion.

A systematic review of teleophthalmological studies in Europe.

A systematic review of the recent literature regarding a series of ocular diseases involved in European telemedicine projects was performed based on the PubMed, Google Scholar and Springer databases in June 2017. Literature review returned 44 eligible studies; among them, emergency ophthalmology, diabetic retinopathy, glaucoma, age-related macular disease, cataract and retinopathy of prematurity. The majority of studies indicate teleophthalmology as a valid, reliable and cost-efficient method for care-provision in ophthalmology patients which delivers comparable outcomes to the traditional examination methods.

A systematic review of pseudophakic monovision for presbyopia correction.

A systematic review of the recent literature regarding pseudophakic monovision as a reliable methods for presbyopia correction was performed based on the PubMed, MEDLINE, Nature and the American Academy of Ophthalmology databases in July 2015 and data from 18 descriptive and 12 comparative studies were included in this narrative review. Pseudophakic monosvision seems to be an effective method for presbyopia with high rates of spectacles independence and minimal dysphotopsia side-effects, that should be considered by the modern cataract surgeons.

Evaluation of activities of daily living following pseudophakic presbyopic correction.

BACKGROUND: Pseudophakic presbyopic correction is among the prevalent methods for regaining near vision capacity. The purpose of this study is to compare the impact of pseudophakic monovision correction and multifocal lens implantation on the performance in a series of activities of daily living (ADL) of presbyopic patients. METHODS: An ADL research framework (10 ADLs) was constructed and validated in a sample of patients divided into three validation groups according to their near visual acuity. Sixty-two participants that underwent mini-monovision (MoG) cataract extraction and 60 that underwent bilateral multifocal lenses implantation (MfG) populated study groups and addressed the ADLs. Binocular uncorrected distant (BdUVA) and near (BnUVA) visual acuity were associated with ADL scores and with subjective satisfaction using the VF-14 questionnaire. RESULTS: Test-retest reliability [all Intraclass Correlations Coefficients (ICC) >0.90] and construct validity (all p < 0.05) tests indicated sufficient psychometric performance of the ADL framework. Both study groups presented comparable mean ADL scores (p = 0.07) however, MoG patients had lower performance in demanding ADLs (p = 0.02). ADL scores demonstrated significant correlation with BnUVA (r2 = -0.67, p < 0.01) VF-14 scores (r2 = 0.53, p < 0.01). CONCLUSIONS: Both methods provide sufficient near vision capacity for the majority of activities of daily living. However, only multifocal lens implantation can address demanding near vision tasks. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02431156.

Impact of corneal cross-linking combined with photorefractive keratectomy on blurring strength.

PURPOSE: The aim of this study was to evaluate the impact of corneal cross-linking combined with photorefractive keratectomy (PRK) on blurring strength. METHODS: A total of 63 patients with keratoconus were recruited for this study, and two study groups were formed according to the therapeutic intervention: corneal collagen cross-linking (CxL) group (33 patients) received corneal cross-linking according to the Dresden protocol, while the rest additionally received topography-guided photorefractive keratectomy (tCxL). The impact of surgical procedure on blurring strength was assessed by power vector analysis. Potential association between blurring strength and vision-specific quality of life was assessed using the National Eye Institute Visual Function Questionnaire (NEI-VFQ) 25 instrument. RESULTS: Blurring strength presented excellent correlation with NEI-VFQ scores both preoperatively and postoperatively (all P<0.01). Both groups demonstrated nonsignificant changes in best-corrected visual acuity; however, only the tCxL group had significant reduction in blurring strength (13.48+10.86 [preoperative], 4.26+7.99 [postoperative], P=0.042). CONCLUSION: Only the combined treatment (tCxL) resulted in significant reduction in blurring strength. Moreover, the excellent correlation of blurring strength with NEI-VFQ scores indicates its reliability as an index of self-reported quality of life in keratoconus, since it seems to address the nonsignificant changes in best-corrected visual acuity following CxL treatments that are conceived as subjective improvement by the patient.

Liquefaction for cataract extraction.

A systematic review of the recent literature regarding the implementation of the liquefaction in cataract surgery and its short-term and long-term outcomes in various parameters that affect the quality of patients' life, including visual rehabilitation and possible complications was performed based on the PubMed, Medline, Nature and the American Academy of Ophthalmology databases in November 2013 and data from 14 comparative studies were included in this narrative review. Liquefaction is an innovative technology for cataract extraction that uses micropulses of balanced salt solution to liquefy the lens nucleus. Most studies reported that liquefaction is a reliable technology for mild to moderate cataracts, while fragmentation difficulties may be encountered with harder nuclei.

Variability of different reference bodies in normal, keratoconus, and collagen crosslinked corneas.

PURPOSE: To evaluate the reproducibility of different Scheimpflug imaging-derived reference bodies in normal, keratoconus (KC), and crosslinked (CXL) eyes. METHODS: In this prospective, observational study, 40 participants populated the control group (CG), while 33 and 34 patients formed the KC group and the CXL group, respectively. One eye was randomly selected when both were eligible. Elevation measurements were obtained using Scheimpflug camera, by applying the following reference bodies: the best fit sphere (BFS), the best fit toric ellipsoid (BFTE), the best fit toric ellipsoid with fixed eccentricity of 0.4 (BFTEF), the best fit ellipsoid (BFE), and the best fit torus, by 2 operators in 2 sessions. The variability of different reference bodies' parameters was assessed using intraclass correlation coefficient (ICC). RESULTS: Differences between operators were nonsignificant for all reference bodies' parameters in all study groups (p>0.1). Regarding CG, BFS for both operators and BFTE for operator 1 presented the best intrasession repeatability (majority of ICCs >0.90), while average interobserver reliability was recorded for the majority of reference bodies' parameters. Regarding KC and CXL groups, BFS, BFTEF, and BFE reference bodies demonstrated the best intrasession and interobserver reproducibility (majority of ICCs >0.90) for both groups. Steep and flat radius parameters presented the best overall reproducibility, with the majority of ICCs for all reference bodies ranging above 0.90, in all study groups. CONCLUSIONS: High variability was encountered for most reference surfaces. Ellipsotoric surfaces presented acceptable repeatability in KC and post-CXL corneas.

Mini-monovision versus multifocal intraocular lens implantation.

PURPOSE: To compare the effect of monovision correction and multifocal intraocular lens (IOL) implantation on patient satisfaction, spectacle dependence, visual acuity, and dysphotopsia in cataract patients. SETTING: University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece. DESIGN: Prospective randomized trial. METHODS: Patients with a diagnosis of senile cataract with stage 2 nuclear opalescence were randomly assigned to 2 groups: monovision and multifocal IOL implantation. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, Visual Function Index-14 (VF-14) scores, and spectacle dependence were assessed prior to surgery and 6 months postoperatively. RESULTS: The monovision group comprised 38 patients and the multifocal IOL implantation group, 37 patients. Both techniques provided excellent refractive outcomes in UDVA and VF-14 scores (all P < .01). No significant intergroup differences were detected in VF-14 scores at the final postoperative examination. The monovision group patients presented significantly more spectacle dependence for near vision but less glare. CONCLUSIONS: Monovision and multifocal IOL implantation provided excellent refractive outcomes for distance vision. Multifocal IOL insertion was associated with less dependence on glasses overall but significantly more dysphotopsia. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Lacrimal outflow mechanisms and the role of scintigraphy: current trends.

Lacrimal outflow can be compromised by anatomical obstructions or stenoses (nonfunctional epiphora) or by defective lacrimal "pump" function (functional epiphora). Although classic imaging modalities, such as X-ray dacryocystography, computed tomography, or magnetic resonance imaging can effectively evaluate the former, their success is much less in the evaluation of the latter. This is largely due to the fact that forced diagnostic injection of fluid into the canalicular system can overcome partial obstruction sites. On the other hand, lacrimal scintigraphy mimicks "physiological" lacrimal outflow, being performed under pressure gradients present in everyday life. This is why it is considered more suitable for the study of functional epiphora. Furthermore, quantitative lacrimal scintigraphy (with time-activity curves) enables the accurate measurement of lacrimal clearance from the conjunctival fornices and may be used to study the physiology of the lacrimal "pump." Data obtained from the scintigraphic study of lacrimal outflow may be used to design more effective procedures in the management of functional and nonfunctional epiphora. This is a review article, based on a literature search with emphasis on recent publications and on those supporting interdisciplinary cooperation between ophthalmology and nuclear medicine.

Corneal collagen cross-linking in a late-onset graft infectious ulcer: a case report.

INTRODUCTION: Infectious keratitis following penetrating keratoplasty is a common postoperative complication. Intensive topical and systemic treatments do not always prevent the risk of graft failure. In this report we demonstrate the beneficial anti-microbial effect of corneal collagen cross-linking in a late-onset, sight-threatening, corneal graft ulcer. CASE PRESENTATION: A 57-year old Caucasian man underwent penetrating keratoplasty in his left eye, due to corneal bullosa after cataract extraction surgery. Twelve months after the penetrating keratoplasty, he visited our emergency service complaining of burning and foreign body sensation in his operated eye. Slit-lamp examination revealed a central, round-shaped ulcer of the graft. Due to poor response to the intensive topical antibiotic therapy, corneal collagen cross-linking was applied 3 days after admission, in an attempt to control the infection. Cultures indicated the predominance of methicillin-resistant Staphylococcus aureus infection. Five days after corneal collagen cross-linking treatment, the epithelium was completely re-epithelized, while the transparency of the transplanted cornea was gradually restored within the 12-month follow-up period. No relapses occurred. CONCLUSION: Corneal collagen cross-linking seems to be a safe and effective therapeutic alternative in resistant cases of infectious keratitis following penetrating keratoplasty.

An overview of corneal collagen cross-linking (CXL).

Corneal collagen cross-linking (CXL) was first described over a decade ago and is now considered to be one of the most important surgical innovations of modern ophthalmology. Prior to its introduction, no interventions were available to arrest, or slow down ectatic disease progression, with corneal transplantation required in the majority of cases. Unlike earlier treatments of corneal ectasias that attempted to only improve the consequences of the disease, CXL aims to address the corneal biomechanical weakening itself. The long-term safety and efficacy of CXL have been established in several studies that have documented significant improvements in all outcome measures (visual acuity, spherical equivalent, astigmatism, and keratometric findings). The emerging combination of CXL with other interventions (termed 'CXL plus') optimizes the visual and topographic outcomes. This, along with the expansion of the techniques' indications for other clinical conditions, such as microbial keratitis, highlights the continuous improvement of the initial technique and confirms its wide acceptance. Overall, CXL has already demonstrated much promise and has several clinical indications, representing a clear example of recent advances in ocular therapy.

Liquefaction versus torsional IP: a comparative study on endothelial cells, corneal edema and corneal sensitivity.

BACKGROUND/AIMS: To compare the impact of liquefaction and torsional IP cataract extraction methods on endothelial cell count (ECC), central corneal edema, and central corneal sensitivity (CCS) in a sample of cataract patients. METHODS: The liquefaction (LG) and torsional IP (TG) group consisted of 47 and 48 grade 2 cataract eyes, respectively. Uncorrected and best spectacle-corrected visual acuity, ECC, central corneal thickness (CCT), and CCS were measured 1 day prior to surgery, 10 days, 1 and 3 months postoperatively. RESULTS: Significant difficulties in the nucleus fragmentation were encountered in 2 LG eyes, and they were excluded from the study. Both techniques provided excellent refractive outcomes (LG, p < 0.001; TG, p = 0.02). Nonsignificant differences were detected in CCT values at the final postoperative examination; however, TG patients presented higher CCT on the first postoperative day (p = 0.04). Both groups presented comparable significant reductions in ECC (LG, p < 0.001; TG, p < 0.001) and CCS (LG, p = 0.02; TG, p = 0.02). CONCLUSION: Both methods provide excellent refractive outcomes, with comparable impact on ECC and CCS. Liquefaction seems to provide less corneal edema; however, difficulties in nucleus fragmentation may be encountered even in grade 2 cataracts.

Tissue inhibitor of metalloproteinase 4 in aqueous humor of patients with primary open angle glaucoma, pseudoexfoliation syndrome and pseudoexfoliative glaucoma and its role in proteolysis imbalance.

BACKGROUND: To quantify the levels of tissue inhibitor of metalloproteinase 4 (TIMP4) and its ratios with free metalloproteinases (MMP) in the aqueous humor of patients with primary open angle glaucoma (POAG), pseudoexfoliation syndrome (PXS) and pseudoexfoliative glaucoma (PXG) and to evaluate a possible imbalance between MMPs and TIMPs in these samples. METHODS: Free MMP2, MMP3, MMP9, TIMP1, TIMP2, TIMP4 concentrations and active levels of MMP2 and MMP3 were determined with immunoassay ELISA and activity assay kits in 168 aqueous samples. RESULTS: TIMP4 was elevated in glaucoma patients(POAG: 0.95 ± 0.49 PXG: 1.28 ± 1.38 pg/ml. p < 0.001). POAG, PXS and PXG samples demonstrated higher MMP2, TIMP1 and TIMP2 concentrations (p < 0.001). Samples from the PXS and PXG groups had a lower total/active MMP2 ratio (p < 0.004 and p < 0.008 respectively). Stoichiometric analysis showed an overbalance of TIMPsover MMPs in both POAG & PXG groups,especially of TIMP4. CONCLUSION: TIMP4 elevation is a novel finding in glaucomatous eyes. A disregulation of extracellular matrix homeostasis is suggested in POAG, PXS and PXG.