alina popa cherecheanu | University of Medicine and Pharmacy "Carol Davila" Bucharest (original) (raw)

Papers by alina popa cherecheanu

Research paper thumbnail of Noninfectious Intermediate, Posterior, or Panuveitis: Results from the Retrospective, Observational, International EyeCOPE Study

Ophthalmology and Therapy, 2021

The EyeCOPE study characterized noninfectious intermediate posterior, or panuveitis (NIIPPU) befo... more The EyeCOPE study characterized noninfectious intermediate posterior, or panuveitis (NIIPPU) before biologic agents were widely available. This retrospective, observational study included adults with NIIPPU attending a routine ophthalmological visit. Data were collected from the study visit and medical records. Of 565 patients, 58.8% were female, and the mean age was 41.3 years; 33.8% had idiopathic uveitis and 45.8% had panuveitis. The median time from symptom onset to diagnosis and treatment was 27.0 and 30.5 days, respectively. Patients received immunosuppressants and systemic/local corticosteroids. Most patients experienced substantial decline in ocular function (mean best corrected visual acuity, 0.4 logMAR). Mean total work productivity impairment among employed patients was 31.0%. Most patients reported ocular complications (70.8%) such as vision loss and cataracts. Despite treatment, most patients with NIIPPU experienced a decline in ocular function and ocular complications....

Research paper thumbnail of Assessment of Clinical and Imagistic Structural Progression in Glaucoma

PubMed, Mar 17, 2016

Glaucoma is a progressive optic neuropathy, characterized by loss of retinal ganglion cells and r... more Glaucoma is a progressive optic neuropathy, characterized by loss of retinal ganglion cells and retinal nerve fiber layer as well as visual field loss. Therefore, in glaucoma, the correlation between structure and function is important, since it can be useful for tracking glaucomatous changes and for following the progression of the disease.

Research paper thumbnail of Serum Neurofilaments and OCT Metrics Predict EDSS-Plus Score Progression in Early Relapse-Remitting Multiple Sclerosis

Biomedicines

(1) Background: Early disability accrual in RRMS patients is frequent and is associated with wors... more (1) Background: Early disability accrual in RRMS patients is frequent and is associated with worse long-term prognosis. Correctly identifying the patients that present a high risk of early disability progression is of utmost importance, and may be aided by the use of predictive biomarkers. (2) Methods: We performed a prospective cohort study that included newly diagnosed RRMS patients, with a minimum follow-up period of one year. Biomarker samples were collected at baseline, 3-, 6-and 12-month follow-ups. Disability progression was measured using the EDSSplus score. (3) Results: A logistic regression model based on baseline and 6-month follow-up sNfL z-scores, RNFL and GCL-IPL thickness and BREMSO score was statistically significant, with χ2(4) = 19.542, p < 0.0001, R2 = 0.791. The model correctly classified 89.1% of cases, with a sensitivity of 80%, a specificity of 93.5%, a positive predictive value of 85.7% and a negative predictive value of 90.62%. (4) Conclusions: Serum biomarkers (adjusted sNfL z-scores at baseline and 6 months) combined with OCT metrics (RNFL and GCL-IPL layer thickness) and the clinical score BREMSO can accurately predict early disability progression using the EDSS-plus score for newly diagnosed RRMS patients.

Research paper thumbnail of Evaluation of Generative Adversarial Networks for High-Resolution Synthetic Image Generation of Circumpapillary Optical Coherence Tomography Images for Glaucoma

JAMA Ophthalmology

ImportanceDeep learning (DL) networks require large data sets for training, which can be challeng... more ImportanceDeep learning (DL) networks require large data sets for training, which can be challenging to collect clinically. Generative models could be used to generate large numbers of synthetic optical coherence tomography (OCT) images to train such DL networks for glaucoma detection.ObjectiveTo assess whether generative models can synthesize circumpapillary optic nerve head OCT images of normal and glaucomatous eyes and determine the usability of synthetic images for training DL models for glaucoma detection.Design, Setting, and ParticipantsProgressively growing generative adversarial network models were trained to generate circumpapillary OCT scans. Image gradeability and authenticity were evaluated on a clinical set of 100 real and 100 synthetic images by 2 clinical experts. DL networks for glaucoma detection were trained with real or synthetic images and evaluated on independent internal and external test data sets of 140 and 300 real images, respectively.Main Outcomes and Meas...

Research paper thumbnail of Microvascular changes in the macular and parafoveal areas of multiple sclerosis patients without optic neuritis

Scientific Reports

Retinal imaging has been proposed as a biomarker for neurological diseases such as multiple scler... more Retinal imaging has been proposed as a biomarker for neurological diseases such as multiple sclerosis (MS). Recently, a technique for non-invasive assessment of the retinal microvasculature called optical coherence tomography angiography (OCTA) was introduced. We investigated retinal microvasculature alterations in participants with relapsing–remitting MS (RRMS) without history of optic neuritis (ON) and compared them to a healthy control group. The study was performed in a prospective, case–control design, including 58 participants (n = 100 eyes) with RRMS without ON and 78 age- and sex-matched control participants (n = 136 eyes). OCTA images of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris (CC) were obtained using a commercial OCTA system (Zeiss Cirrus HD-5000 Spectral-Domain OCT with AngioPlex OCTA, Carl Zeiss Meditec, Dublin, CA). The outcome variables were perfusion density (PD) and foveal avascular zone (FAZ) features (area and circul...

Research paper thumbnail of Biocompatible Materials for Orbital Wall Reconstruction—An Overview

Materials, 2022

The reconstruction of an orbit after complex craniofacial fractures can be extremely demanding. F... more The reconstruction of an orbit after complex craniofacial fractures can be extremely demanding. For satisfactory functional and aesthetic results, it is necessary to restore the orbital walls and the craniofacial skeleton using various types of materials. The reconstruction materials can be divided into autografts (bone or cartilage tissue) or allografts (metals, ceramics, or plastic materials, and combinations of these materials). Over time, different types of materials have been used, considering characteristics such as their stability, biocompatibility, cost, safety, and intraoperative flexibility. Although the ideal material for orbital reconstruction could not be unanimously identified, much progress has been achieved in recent years. In this article, we summarise the advantages and disadvantages of each category of reconstruction materials. We also provide an update on improvements in material properties through various modern processing techniques. Good results in reconstruct...

Research paper thumbnail of Bacterial Resistance in Ophthalmology – Resistance Profile, Influencing Factors and Prevention Methods. A Review

Modern Medicine, Jun 30, 2021

Ocular infections vary greatly in severity. Studies have tried to identify certain patterns relat... more Ocular infections vary greatly in severity. Studies have tried to identify certain patterns related to the ocular microbiome in the studied populations in order to identify risk populations, new treatments and prophylaxis guidelines. However, it is critical to determine which antibiotics should be used in various situations and where alternatives to antibiotics are appropriate. Results of many studies show that high levels of antibiotic resistance in ophthalmology and multidrug resistance continue to be a reality and a challenge today. Iodine-povidone and chlorhexidine are two major antiseptics used in ophthalmology. It is hoped that future reports show good results without the use of antibiotics will encourage ophthalmologists to limit the use of topical antibiotics, reducing the rate of antimicrobial resistance.

Research paper thumbnail of Outcomes of Diabetic Retinopathy Post-Bariatric Surgery in Patients with Type 2 Diabetes Mellitus

Journal of Clinical Medicine, 2021

Bariatric surgery is an emerging therapeutic approach for obese type 2 diabetes mellitus (T2DM) p... more Bariatric surgery is an emerging therapeutic approach for obese type 2 diabetes mellitus (T2DM) patients, with proven benefits for achieving target glucose control and even remission of diabetes. However, the effect of bariatric surgery upon diabetic retinopathy is still a subject of debate as some studies show a positive effect while others raise concerns about potential early worsening effects. We performed a systematic review, on PubMed, Science Direct, and Web of Science databases regarding the onset and progression of diabetic retinopathy in obese T2DM patients who underwent weight-loss surgical procedures. A total of 6375 T2DM patients were analyzed. Most cases remained stable after bariatric surgery (89.6%). New onset of diabetic retinopathy (DR) was documented in 290 out of 5972 patients (4.8%). In cases with DR at baseline, progression was documented in 50 out of 403 (12.4%) and regression in 90 (22.3%). Preoperative careful preparation of hemoglobin A1c (HbA1c), blood pres...

Research paper thumbnail of Docetaxel for Breast Cancer Treatment-Side Effects on Ocular Surface, a Systematic Review

Processes, 2021

Docetaxel is a very effective chemotherapeutic agent for the treatment of metastatic or locally a... more Docetaxel is a very effective chemotherapeutic agent for the treatment of metastatic or locally advanced breast cancer. Epiphora (hyperlacrimation) has been shown to be the most common eye condition in patients receiving docetaxel-based chemotherapy. This symptom does not decrease visual acuity, but decreases the quality of life. Daily activities (reading, working on the computer, watching TV, and so on) are affected, with patients complaining about an alteration of daily life with the appearance of this symptom. The mechanism by which epiphora occurs is considered to be the canalicular stenosis, but the trials on the subject failed to reach statistical significance. The objective of this scoping review is to determine whether there is a treatment regimen-dependent relationship between docetaxel administration and the presence of epiphora in women with breast cancer. The inclusion criteria were met by 10 trials, from which one was excluded owing to data selection biases. Accordingly...

Research paper thumbnail of Hypervirulent Klebsiella pneumoniae Endogenous Endophthalmitis—A Global Emerging Disease

Life, 2021

The review aims to document the new emerging hypervirulent Klebsiella pneumoniae (Kp) endogenous ... more The review aims to document the new emerging hypervirulent Klebsiella pneumoniae (Kp) endogenous endophthalmitis (EKE) in terms of incidence, microbiological characterization of the pathogenic agent, associated risk factors, management, and outcomes. Hypervirulent (hv) strains of KP (hvKp) induce invasive liver abscesses (LA) with specific clinical features. Up to 80–90% of cases have hepatic liver abscess as a primary focus of infection, followed by renal or lung hvKp infections. However, the incidence of EKE in patients with KPLA varied between 3.4% (19) and 12.6% (13), with a total of 95 cases of endophthalmitis in 1455 cases of KPLA (6.5%). Severe visual loss was encountered in 75% of cases, with 25% bilateral involvement. Intravitreal antibiotics are the mainstay therapeutic approach. Pars plana vitrectomy is a subject of controversy. HvKp strains present mostly natural “wild-type” antibiotic resistance profile suggestive for community-acquired infections, being highly suscepti...

Research paper thumbnail of Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye

JAMA, 2021

The Genetics of Exfoliation Syndrome Partnership IMPORTANCE Exfoliation syndrome is a systemic di... more The Genetics of Exfoliation Syndrome Partnership IMPORTANCE Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. OBJECTIVE To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. DESIGN, SETTING, AND PARTICIPANTS A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. EXPOSURES Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. MAIN OUTCOMES AND MEASURES The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10 −6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses. RESULTS The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10 −7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. CONCLUSIONS AND RELEVANCE In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.

Research paper thumbnail of Update on Myopia Risk Factors and Microenvironmental Changes

Journal of Ophthalmology, 2019

The focus of this update is to emphasize the recent advances in the pathogenesis and various mole... more The focus of this update is to emphasize the recent advances in the pathogenesis and various molecular key approaches associated with myopia in order to reveal new potential therapeutic targets. We review the current evidence for its complex genetics and evaluate the known or candidate genes and loci. In addition, we discuss recent investigations regarding the role of environmental factors. This paper also covers current research aimed at elucidating the signaling pathways involved in the pathogenesis of myopia.

Research paper thumbnail of Referral for first glaucoma surgery in Europe, the ReF-GS study

European Journal of Ophthalmology, 2018

Purpose: To analyze the appropriateness of referrals for incisional glaucoma-surgery in Europe. M... more Purpose: To analyze the appropriateness of referrals for incisional glaucoma-surgery in Europe. Methods: Referrals for the first open-angle glaucoma surgery between January and October 2017 were analyzed in 18 countries: 8 “old” European Union, 7 “new” European Union and 3 non-European Union European countries. Results: Most eyes had primary open-angle or exfoliative glaucoma. The average mean deviation was −13.8 dB with split fixation in 44.3%. No structural progression analysis was made before the referrals. The most common medications were the combination of a prostaglandin analog, timolol and a carbonic anhydrase inhibitor (30.0%), and all other combinations comprising ⩾ 3 molecules (33.8%). Laser trabeculoplasty was reported in only 18.4%. Of the 294 referrals, 41.5% were appropriate and timely, 35.0% appropriate but later than optimal, and 17.6% appropriate but too late (minimal vision maintained). The treatment period was significantly longer (median: 7 years) in the “old” Eu...

Research paper thumbnail of Endocannabinoid System and Ocular Vascularization

Nepalese Journal of Ophthalmology, 2018

The focus of this review is the role of endocannabinoid system in ocular and systemic circulation... more The focus of this review is the role of endocannabinoid system in ocular and systemic circulation. By critically examining preclinical and clinical research, we explore the cannabinoid receptors localization and vascular implications as well as their interaction with other anti-inflammatory drugs. The objective is to transfer knowledge on the use of cannabinoids, specifically their effect on ocular circulation and intraocular pressure, and provide a better understanding of the endocannabinoid system complexity in modulating local and systemic circulations in order to identify potential uses and limitations of cannabinoid-based therapeutics.

Research paper thumbnail of Regulation of Choroidal Blood Flow During Isometric Exercise at Different Levels of Intraocular Pressure

Investigative Opthalmology & Visual Science, 2019

PURPOSE. There is evidence that choroidal blood flow (ChBF) is regulated in a complex way during ... more PURPOSE. There is evidence that choroidal blood flow (ChBF) is regulated in a complex way during changes in ocular perfusion pressure (OPP). We hypothesized that ChBF regulates better in response to changes in mean arterial pressure (MAP) than in intraocular pressure (IOP). METHODS. Eighteen volunteers (mean age, 26 years) were recruited for a randomized, threeway crossover design. MAP was varied via isometric exercise. IOP was either kept normal or elevated by 10 or 20 mm Hg by using a suction cup. Subfoveal ChBF was measured continuously for 8 minutes with laser Doppler flowmetry and OPP was calculated as 2/ 3*MAP-IOP. For data analysis, values from all subjects were pooled according to either IOP or MAP values, and correlation analyses were done. RESULTS. When data were grouped according to IOP, no correlation was observed between ChBF and MAP, but ChBF was lower the higher the IOP (P < 0.001). When data were grouped according to MAP, a significant correlation was found between ChBF and IOP (P < 0.001). When data were pooled according to IOP, the correlation between ChBF and OPP was weaker (P < 0.05). The OPP at which ChBF significantly increased from baseline was 61.3% 6 4.9% without suction cup, 65.2% 6 3.5% when IOP was increased by 10 mm Hg, and slightly lower when IOP was increased by 20 mm Hg (56.3% 6 4.8%, P ¼ 0.07), but this effect did not reach the level of significance. CONCLUSIONS. The present study provides further evidence that the regulation of ChBF during changes in OPP is controlled by complex mechanisms in humans and has less capacity to adapt to IOP elevation than to MAP increase.

Research paper thumbnail of Effect of Hyaluronic Acid/Trehalose in Two Different Formulations on Signs and Symptoms in Patients with Moderate to Severe Dry Eye Disease

Journal of ophthalmology, 2018

This randomized, observer-masked, crossover study investigated the effect of two hyaluronic acid/... more This randomized, observer-masked, crossover study investigated the effect of two hyaluronic acid/trehalose-based containing formulations, with different physical properties, on the signs and symptoms in patients with moderate to severe dry eye disease (DED). In one group, patients received a mixture of sodium hyaluronate and trehalose (HT, Thealoz Duo®) for use during the day. In the other group, patients received a more viscous formulation consisting of hyaluronic acid, trehalose, and carbomer (HTC-gel, Thealoz Duo Gel) to use pro re nata. Both groups used HTC-gel before going to bed. Clinical standard tests for DED were performed at the beginning and end of each one-week period. Further, patient satisfaction including quality of sleep was assessed using a visual analogue scale. Corneal fluorescein and conjunctival lissamine green staining scores decreased, and tear breakup time (BUT) increased for both groups ( < 0.001 each). Mean instillation frequency was 3.1 ± 2.6 drops/day ...

Research paper thumbnail of Off-label" use of intravitreal bevacizumab in non-ischemic macular edema secondary to retinal vein obstructions

Romanian journal of ophthalmology

To evaluate the safety and efficacy of intravitreal Bevacizumab in treatment of non-ischemic macu... more To evaluate the safety and efficacy of intravitreal Bevacizumab in treatment of non-ischemic macular edema secondary to retinal vein obstruction (RVO). A 2-year-retrospective study was performed on 26 patients hospitalized for non-ischemic macular edema secondary to RVO. All the patients underwent a complete ophthalmologic exam, with best corrected visual acuity (BCVA) testing, fundus photography, fluorescein angiography (FA) and macular thickness measurement by optical coherence tomography (OCT). Reevaluation was performed monthly for VA, OCT, and ophthalmoscopy and, at every 3 months, by FA. A standard protocol of 0.05 ml intravitreal Bevacizumab injection was applied. Further administrations were performed according to clinical evolution. The medium follow-up period was of 9,7 months (6-20 months). There were no significant complications following the procedure. The number of intravitreal Bevacizumab injections varied from 2-5/ patient. All the patients experienced an improvement...

Research paper thumbnail of Fulminant bilateral acute retinal necrosis after chickenpox - a case report

Romanian journal of ophthalmology

We present the case of a 34-year-old male, admitted for progressive bilateral loss of vision afte... more We present the case of a 34-year-old male, admitted for progressive bilateral loss of vision after a recent episode of chickenpox. Ophthalmological exam revealed bilateral acute retinal necrosis. As the patient was following a drug detoxification program, he was tested for HIV, HVB, HVC, and results highly positive. Immediate intravenous therapy with high doses of acyclovir and methylprednisolone was initiated, but the evolution was extremely severe resulting in necrotic retinal detachment. Surgery was performed in right eye, but no improvement of visual acuity was observed. The fulminant evolution of bilateral acute retinal necrosis and the lack of response to maximal intravenous therapy were clinical elements indicating coexistent immunosuppressive disease. Very severe acute retinal necrosis may occur in immunosuppressed patients, leading to blindness.

Research paper thumbnail of Assessment of choroidal blood flow using laser speckle flowgraphy

The British journal of ophthalmology, Jan 22, 2018

There is considerable interest in novel techniques to quantify choroidal blood flow (CBF) in huma... more There is considerable interest in novel techniques to quantify choroidal blood flow (CBF) in humans. In the present study, we investigated a novel technique to measure CBF based on laser speckle flowgraphy (LSFG) in healthy subjects. This study included 31 eyes of 31 healthy, non-smoking subjects aged between 19 and 74 years. A commercial LSFG instrument was used to measure choroidal vessel diameter (CVD) and relative flow volume (RFV) in choroidal vessels that were identified on fundus photos, an approach that was used previously only for retinal vessels. The reproducibility and the effect of isometric exercise on these parameters were investigated. The latter was compared with measurement of subfoveal CBF using laser Doppler flowmetry (LDF). Intraclass correlation coefficients for CVD and RFV were higher than 0.8 indicating excellent reproducibility. During isometric exercise, we observed an increase in ocular perfusion pressure of approximately 60% (P<0.001). The increase in R...

Research paper thumbnail of Optic nerve head and retinal blood flow regulation during isometric exercise as assessed with laser speckle flowgraphy

PLOS ONE, 2017

The aim of the present study was to investigate regulation of blood flow (BF) in the optic nerve ... more The aim of the present study was to investigate regulation of blood flow (BF) in the optic nerve head (ONH) and a peripapillary region (PPR) during an isometric exercise-induced increase in ocular perfusion pressure (OPP) using laser speckle flowgraphy (LSFG) in healthy subjects. For this purpose, a total of 27 subjects was included in this study. Mean blur rate in tissue (MT) was measured in the ONH and in a PPR as well as relative flow volume (RFV) in retinal arteries (ART) and veins (VEIN) using LSFG. All participants performed isometric exercise for 6 minutes during which MT and mean arterial pressure were measured every minute. From these data OPP and pressure/flow curves were calculated. Isometric exercise increased OPP, MT ONH and MT PRR. The relative increase in OPP (78.5 ± 19.8%) was more pronounced than the increase in BF parameters (MT ONH : 18.1 ± 7.7%, MT PRR : 21.1 ± 8.3%, RFV ART : 16.5 ±12.0%, RFV VEIN : 17.7 ± 12.4%) indicating for an autoregulatory response of the vasculature. The pressure/flow curves show that MT ONH , MT PRR , RFV ART , RFV VEIN started to increase at OPP levels of 51.2 ± 2.0%, 58.1 ± 2.4%, 45.6 ± 1.9% and 45.6 ± 1.9% above baseline. These data indicate that ONHBF starts to increase at levels of approx. 50% increase in OPP: This is slightly lower than the values we previously reported from LDF data. Signals from the PPR may have input from both, the retina and the choroid, but the relative contribution is unknown. In addition, retinal BF appears to increase at slightly lower OPP values of approximately 45%. LSFG may be used to study ONH autoregulation in diseases such as glaucoma.

Research paper thumbnail of Noninfectious Intermediate, Posterior, or Panuveitis: Results from the Retrospective, Observational, International EyeCOPE Study

Ophthalmology and Therapy, 2021

The EyeCOPE study characterized noninfectious intermediate posterior, or panuveitis (NIIPPU) befo... more The EyeCOPE study characterized noninfectious intermediate posterior, or panuveitis (NIIPPU) before biologic agents were widely available. This retrospective, observational study included adults with NIIPPU attending a routine ophthalmological visit. Data were collected from the study visit and medical records. Of 565 patients, 58.8% were female, and the mean age was 41.3 years; 33.8% had idiopathic uveitis and 45.8% had panuveitis. The median time from symptom onset to diagnosis and treatment was 27.0 and 30.5 days, respectively. Patients received immunosuppressants and systemic/local corticosteroids. Most patients experienced substantial decline in ocular function (mean best corrected visual acuity, 0.4 logMAR). Mean total work productivity impairment among employed patients was 31.0%. Most patients reported ocular complications (70.8%) such as vision loss and cataracts. Despite treatment, most patients with NIIPPU experienced a decline in ocular function and ocular complications....

Research paper thumbnail of Assessment of Clinical and Imagistic Structural Progression in Glaucoma

PubMed, Mar 17, 2016

Glaucoma is a progressive optic neuropathy, characterized by loss of retinal ganglion cells and r... more Glaucoma is a progressive optic neuropathy, characterized by loss of retinal ganglion cells and retinal nerve fiber layer as well as visual field loss. Therefore, in glaucoma, the correlation between structure and function is important, since it can be useful for tracking glaucomatous changes and for following the progression of the disease.

Research paper thumbnail of Serum Neurofilaments and OCT Metrics Predict EDSS-Plus Score Progression in Early Relapse-Remitting Multiple Sclerosis

Biomedicines

(1) Background: Early disability accrual in RRMS patients is frequent and is associated with wors... more (1) Background: Early disability accrual in RRMS patients is frequent and is associated with worse long-term prognosis. Correctly identifying the patients that present a high risk of early disability progression is of utmost importance, and may be aided by the use of predictive biomarkers. (2) Methods: We performed a prospective cohort study that included newly diagnosed RRMS patients, with a minimum follow-up period of one year. Biomarker samples were collected at baseline, 3-, 6-and 12-month follow-ups. Disability progression was measured using the EDSSplus score. (3) Results: A logistic regression model based on baseline and 6-month follow-up sNfL z-scores, RNFL and GCL-IPL thickness and BREMSO score was statistically significant, with χ2(4) = 19.542, p < 0.0001, R2 = 0.791. The model correctly classified 89.1% of cases, with a sensitivity of 80%, a specificity of 93.5%, a positive predictive value of 85.7% and a negative predictive value of 90.62%. (4) Conclusions: Serum biomarkers (adjusted sNfL z-scores at baseline and 6 months) combined with OCT metrics (RNFL and GCL-IPL layer thickness) and the clinical score BREMSO can accurately predict early disability progression using the EDSS-plus score for newly diagnosed RRMS patients.

Research paper thumbnail of Evaluation of Generative Adversarial Networks for High-Resolution Synthetic Image Generation of Circumpapillary Optical Coherence Tomography Images for Glaucoma

JAMA Ophthalmology

ImportanceDeep learning (DL) networks require large data sets for training, which can be challeng... more ImportanceDeep learning (DL) networks require large data sets for training, which can be challenging to collect clinically. Generative models could be used to generate large numbers of synthetic optical coherence tomography (OCT) images to train such DL networks for glaucoma detection.ObjectiveTo assess whether generative models can synthesize circumpapillary optic nerve head OCT images of normal and glaucomatous eyes and determine the usability of synthetic images for training DL models for glaucoma detection.Design, Setting, and ParticipantsProgressively growing generative adversarial network models were trained to generate circumpapillary OCT scans. Image gradeability and authenticity were evaluated on a clinical set of 100 real and 100 synthetic images by 2 clinical experts. DL networks for glaucoma detection were trained with real or synthetic images and evaluated on independent internal and external test data sets of 140 and 300 real images, respectively.Main Outcomes and Meas...

Research paper thumbnail of Microvascular changes in the macular and parafoveal areas of multiple sclerosis patients without optic neuritis

Scientific Reports

Retinal imaging has been proposed as a biomarker for neurological diseases such as multiple scler... more Retinal imaging has been proposed as a biomarker for neurological diseases such as multiple sclerosis (MS). Recently, a technique for non-invasive assessment of the retinal microvasculature called optical coherence tomography angiography (OCTA) was introduced. We investigated retinal microvasculature alterations in participants with relapsing–remitting MS (RRMS) without history of optic neuritis (ON) and compared them to a healthy control group. The study was performed in a prospective, case–control design, including 58 participants (n = 100 eyes) with RRMS without ON and 78 age- and sex-matched control participants (n = 136 eyes). OCTA images of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris (CC) were obtained using a commercial OCTA system (Zeiss Cirrus HD-5000 Spectral-Domain OCT with AngioPlex OCTA, Carl Zeiss Meditec, Dublin, CA). The outcome variables were perfusion density (PD) and foveal avascular zone (FAZ) features (area and circul...

Research paper thumbnail of Biocompatible Materials for Orbital Wall Reconstruction—An Overview

Materials, 2022

The reconstruction of an orbit after complex craniofacial fractures can be extremely demanding. F... more The reconstruction of an orbit after complex craniofacial fractures can be extremely demanding. For satisfactory functional and aesthetic results, it is necessary to restore the orbital walls and the craniofacial skeleton using various types of materials. The reconstruction materials can be divided into autografts (bone or cartilage tissue) or allografts (metals, ceramics, or plastic materials, and combinations of these materials). Over time, different types of materials have been used, considering characteristics such as their stability, biocompatibility, cost, safety, and intraoperative flexibility. Although the ideal material for orbital reconstruction could not be unanimously identified, much progress has been achieved in recent years. In this article, we summarise the advantages and disadvantages of each category of reconstruction materials. We also provide an update on improvements in material properties through various modern processing techniques. Good results in reconstruct...

Research paper thumbnail of Bacterial Resistance in Ophthalmology – Resistance Profile, Influencing Factors and Prevention Methods. A Review

Modern Medicine, Jun 30, 2021

Ocular infections vary greatly in severity. Studies have tried to identify certain patterns relat... more Ocular infections vary greatly in severity. Studies have tried to identify certain patterns related to the ocular microbiome in the studied populations in order to identify risk populations, new treatments and prophylaxis guidelines. However, it is critical to determine which antibiotics should be used in various situations and where alternatives to antibiotics are appropriate. Results of many studies show that high levels of antibiotic resistance in ophthalmology and multidrug resistance continue to be a reality and a challenge today. Iodine-povidone and chlorhexidine are two major antiseptics used in ophthalmology. It is hoped that future reports show good results without the use of antibiotics will encourage ophthalmologists to limit the use of topical antibiotics, reducing the rate of antimicrobial resistance.

Research paper thumbnail of Outcomes of Diabetic Retinopathy Post-Bariatric Surgery in Patients with Type 2 Diabetes Mellitus

Journal of Clinical Medicine, 2021

Bariatric surgery is an emerging therapeutic approach for obese type 2 diabetes mellitus (T2DM) p... more Bariatric surgery is an emerging therapeutic approach for obese type 2 diabetes mellitus (T2DM) patients, with proven benefits for achieving target glucose control and even remission of diabetes. However, the effect of bariatric surgery upon diabetic retinopathy is still a subject of debate as some studies show a positive effect while others raise concerns about potential early worsening effects. We performed a systematic review, on PubMed, Science Direct, and Web of Science databases regarding the onset and progression of diabetic retinopathy in obese T2DM patients who underwent weight-loss surgical procedures. A total of 6375 T2DM patients were analyzed. Most cases remained stable after bariatric surgery (89.6%). New onset of diabetic retinopathy (DR) was documented in 290 out of 5972 patients (4.8%). In cases with DR at baseline, progression was documented in 50 out of 403 (12.4%) and regression in 90 (22.3%). Preoperative careful preparation of hemoglobin A1c (HbA1c), blood pres...

Research paper thumbnail of Docetaxel for Breast Cancer Treatment-Side Effects on Ocular Surface, a Systematic Review

Processes, 2021

Docetaxel is a very effective chemotherapeutic agent for the treatment of metastatic or locally a... more Docetaxel is a very effective chemotherapeutic agent for the treatment of metastatic or locally advanced breast cancer. Epiphora (hyperlacrimation) has been shown to be the most common eye condition in patients receiving docetaxel-based chemotherapy. This symptom does not decrease visual acuity, but decreases the quality of life. Daily activities (reading, working on the computer, watching TV, and so on) are affected, with patients complaining about an alteration of daily life with the appearance of this symptom. The mechanism by which epiphora occurs is considered to be the canalicular stenosis, but the trials on the subject failed to reach statistical significance. The objective of this scoping review is to determine whether there is a treatment regimen-dependent relationship between docetaxel administration and the presence of epiphora in women with breast cancer. The inclusion criteria were met by 10 trials, from which one was excluded owing to data selection biases. Accordingly...

Research paper thumbnail of Hypervirulent Klebsiella pneumoniae Endogenous Endophthalmitis—A Global Emerging Disease

Life, 2021

The review aims to document the new emerging hypervirulent Klebsiella pneumoniae (Kp) endogenous ... more The review aims to document the new emerging hypervirulent Klebsiella pneumoniae (Kp) endogenous endophthalmitis (EKE) in terms of incidence, microbiological characterization of the pathogenic agent, associated risk factors, management, and outcomes. Hypervirulent (hv) strains of KP (hvKp) induce invasive liver abscesses (LA) with specific clinical features. Up to 80–90% of cases have hepatic liver abscess as a primary focus of infection, followed by renal or lung hvKp infections. However, the incidence of EKE in patients with KPLA varied between 3.4% (19) and 12.6% (13), with a total of 95 cases of endophthalmitis in 1455 cases of KPLA (6.5%). Severe visual loss was encountered in 75% of cases, with 25% bilateral involvement. Intravitreal antibiotics are the mainstay therapeutic approach. Pars plana vitrectomy is a subject of controversy. HvKp strains present mostly natural “wild-type” antibiotic resistance profile suggestive for community-acquired infections, being highly suscepti...

Research paper thumbnail of Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye

JAMA, 2021

The Genetics of Exfoliation Syndrome Partnership IMPORTANCE Exfoliation syndrome is a systemic di... more The Genetics of Exfoliation Syndrome Partnership IMPORTANCE Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. OBJECTIVE To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. DESIGN, SETTING, AND PARTICIPANTS A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. EXPOSURES Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. MAIN OUTCOMES AND MEASURES The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10 −6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses. RESULTS The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10 −7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. CONCLUSIONS AND RELEVANCE In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.

Research paper thumbnail of Update on Myopia Risk Factors and Microenvironmental Changes

Journal of Ophthalmology, 2019

The focus of this update is to emphasize the recent advances in the pathogenesis and various mole... more The focus of this update is to emphasize the recent advances in the pathogenesis and various molecular key approaches associated with myopia in order to reveal new potential therapeutic targets. We review the current evidence for its complex genetics and evaluate the known or candidate genes and loci. In addition, we discuss recent investigations regarding the role of environmental factors. This paper also covers current research aimed at elucidating the signaling pathways involved in the pathogenesis of myopia.

Research paper thumbnail of Referral for first glaucoma surgery in Europe, the ReF-GS study

European Journal of Ophthalmology, 2018

Purpose: To analyze the appropriateness of referrals for incisional glaucoma-surgery in Europe. M... more Purpose: To analyze the appropriateness of referrals for incisional glaucoma-surgery in Europe. Methods: Referrals for the first open-angle glaucoma surgery between January and October 2017 were analyzed in 18 countries: 8 “old” European Union, 7 “new” European Union and 3 non-European Union European countries. Results: Most eyes had primary open-angle or exfoliative glaucoma. The average mean deviation was −13.8 dB with split fixation in 44.3%. No structural progression analysis was made before the referrals. The most common medications were the combination of a prostaglandin analog, timolol and a carbonic anhydrase inhibitor (30.0%), and all other combinations comprising ⩾ 3 molecules (33.8%). Laser trabeculoplasty was reported in only 18.4%. Of the 294 referrals, 41.5% were appropriate and timely, 35.0% appropriate but later than optimal, and 17.6% appropriate but too late (minimal vision maintained). The treatment period was significantly longer (median: 7 years) in the “old” Eu...

Research paper thumbnail of Endocannabinoid System and Ocular Vascularization

Nepalese Journal of Ophthalmology, 2018

The focus of this review is the role of endocannabinoid system in ocular and systemic circulation... more The focus of this review is the role of endocannabinoid system in ocular and systemic circulation. By critically examining preclinical and clinical research, we explore the cannabinoid receptors localization and vascular implications as well as their interaction with other anti-inflammatory drugs. The objective is to transfer knowledge on the use of cannabinoids, specifically their effect on ocular circulation and intraocular pressure, and provide a better understanding of the endocannabinoid system complexity in modulating local and systemic circulations in order to identify potential uses and limitations of cannabinoid-based therapeutics.

Research paper thumbnail of Regulation of Choroidal Blood Flow During Isometric Exercise at Different Levels of Intraocular Pressure

Investigative Opthalmology & Visual Science, 2019

PURPOSE. There is evidence that choroidal blood flow (ChBF) is regulated in a complex way during ... more PURPOSE. There is evidence that choroidal blood flow (ChBF) is regulated in a complex way during changes in ocular perfusion pressure (OPP). We hypothesized that ChBF regulates better in response to changes in mean arterial pressure (MAP) than in intraocular pressure (IOP). METHODS. Eighteen volunteers (mean age, 26 years) were recruited for a randomized, threeway crossover design. MAP was varied via isometric exercise. IOP was either kept normal or elevated by 10 or 20 mm Hg by using a suction cup. Subfoveal ChBF was measured continuously for 8 minutes with laser Doppler flowmetry and OPP was calculated as 2/ 3*MAP-IOP. For data analysis, values from all subjects were pooled according to either IOP or MAP values, and correlation analyses were done. RESULTS. When data were grouped according to IOP, no correlation was observed between ChBF and MAP, but ChBF was lower the higher the IOP (P < 0.001). When data were grouped according to MAP, a significant correlation was found between ChBF and IOP (P < 0.001). When data were pooled according to IOP, the correlation between ChBF and OPP was weaker (P < 0.05). The OPP at which ChBF significantly increased from baseline was 61.3% 6 4.9% without suction cup, 65.2% 6 3.5% when IOP was increased by 10 mm Hg, and slightly lower when IOP was increased by 20 mm Hg (56.3% 6 4.8%, P ¼ 0.07), but this effect did not reach the level of significance. CONCLUSIONS. The present study provides further evidence that the regulation of ChBF during changes in OPP is controlled by complex mechanisms in humans and has less capacity to adapt to IOP elevation than to MAP increase.

Research paper thumbnail of Effect of Hyaluronic Acid/Trehalose in Two Different Formulations on Signs and Symptoms in Patients with Moderate to Severe Dry Eye Disease

Journal of ophthalmology, 2018

This randomized, observer-masked, crossover study investigated the effect of two hyaluronic acid/... more This randomized, observer-masked, crossover study investigated the effect of two hyaluronic acid/trehalose-based containing formulations, with different physical properties, on the signs and symptoms in patients with moderate to severe dry eye disease (DED). In one group, patients received a mixture of sodium hyaluronate and trehalose (HT, Thealoz Duo®) for use during the day. In the other group, patients received a more viscous formulation consisting of hyaluronic acid, trehalose, and carbomer (HTC-gel, Thealoz Duo Gel) to use pro re nata. Both groups used HTC-gel before going to bed. Clinical standard tests for DED were performed at the beginning and end of each one-week period. Further, patient satisfaction including quality of sleep was assessed using a visual analogue scale. Corneal fluorescein and conjunctival lissamine green staining scores decreased, and tear breakup time (BUT) increased for both groups ( < 0.001 each). Mean instillation frequency was 3.1 ± 2.6 drops/day ...

Research paper thumbnail of Off-label" use of intravitreal bevacizumab in non-ischemic macular edema secondary to retinal vein obstructions

Romanian journal of ophthalmology

To evaluate the safety and efficacy of intravitreal Bevacizumab in treatment of non-ischemic macu... more To evaluate the safety and efficacy of intravitreal Bevacizumab in treatment of non-ischemic macular edema secondary to retinal vein obstruction (RVO). A 2-year-retrospective study was performed on 26 patients hospitalized for non-ischemic macular edema secondary to RVO. All the patients underwent a complete ophthalmologic exam, with best corrected visual acuity (BCVA) testing, fundus photography, fluorescein angiography (FA) and macular thickness measurement by optical coherence tomography (OCT). Reevaluation was performed monthly for VA, OCT, and ophthalmoscopy and, at every 3 months, by FA. A standard protocol of 0.05 ml intravitreal Bevacizumab injection was applied. Further administrations were performed according to clinical evolution. The medium follow-up period was of 9,7 months (6-20 months). There were no significant complications following the procedure. The number of intravitreal Bevacizumab injections varied from 2-5/ patient. All the patients experienced an improvement...

Research paper thumbnail of Fulminant bilateral acute retinal necrosis after chickenpox - a case report

Romanian journal of ophthalmology

We present the case of a 34-year-old male, admitted for progressive bilateral loss of vision afte... more We present the case of a 34-year-old male, admitted for progressive bilateral loss of vision after a recent episode of chickenpox. Ophthalmological exam revealed bilateral acute retinal necrosis. As the patient was following a drug detoxification program, he was tested for HIV, HVB, HVC, and results highly positive. Immediate intravenous therapy with high doses of acyclovir and methylprednisolone was initiated, but the evolution was extremely severe resulting in necrotic retinal detachment. Surgery was performed in right eye, but no improvement of visual acuity was observed. The fulminant evolution of bilateral acute retinal necrosis and the lack of response to maximal intravenous therapy were clinical elements indicating coexistent immunosuppressive disease. Very severe acute retinal necrosis may occur in immunosuppressed patients, leading to blindness.

Research paper thumbnail of Assessment of choroidal blood flow using laser speckle flowgraphy

The British journal of ophthalmology, Jan 22, 2018

There is considerable interest in novel techniques to quantify choroidal blood flow (CBF) in huma... more There is considerable interest in novel techniques to quantify choroidal blood flow (CBF) in humans. In the present study, we investigated a novel technique to measure CBF based on laser speckle flowgraphy (LSFG) in healthy subjects. This study included 31 eyes of 31 healthy, non-smoking subjects aged between 19 and 74 years. A commercial LSFG instrument was used to measure choroidal vessel diameter (CVD) and relative flow volume (RFV) in choroidal vessels that were identified on fundus photos, an approach that was used previously only for retinal vessels. The reproducibility and the effect of isometric exercise on these parameters were investigated. The latter was compared with measurement of subfoveal CBF using laser Doppler flowmetry (LDF). Intraclass correlation coefficients for CVD and RFV were higher than 0.8 indicating excellent reproducibility. During isometric exercise, we observed an increase in ocular perfusion pressure of approximately 60% (P<0.001). The increase in R...

Research paper thumbnail of Optic nerve head and retinal blood flow regulation during isometric exercise as assessed with laser speckle flowgraphy

PLOS ONE, 2017

The aim of the present study was to investigate regulation of blood flow (BF) in the optic nerve ... more The aim of the present study was to investigate regulation of blood flow (BF) in the optic nerve head (ONH) and a peripapillary region (PPR) during an isometric exercise-induced increase in ocular perfusion pressure (OPP) using laser speckle flowgraphy (LSFG) in healthy subjects. For this purpose, a total of 27 subjects was included in this study. Mean blur rate in tissue (MT) was measured in the ONH and in a PPR as well as relative flow volume (RFV) in retinal arteries (ART) and veins (VEIN) using LSFG. All participants performed isometric exercise for 6 minutes during which MT and mean arterial pressure were measured every minute. From these data OPP and pressure/flow curves were calculated. Isometric exercise increased OPP, MT ONH and MT PRR. The relative increase in OPP (78.5 ± 19.8%) was more pronounced than the increase in BF parameters (MT ONH : 18.1 ± 7.7%, MT PRR : 21.1 ± 8.3%, RFV ART : 16.5 ±12.0%, RFV VEIN : 17.7 ± 12.4%) indicating for an autoregulatory response of the vasculature. The pressure/flow curves show that MT ONH , MT PRR , RFV ART , RFV VEIN started to increase at OPP levels of 51.2 ± 2.0%, 58.1 ± 2.4%, 45.6 ± 1.9% and 45.6 ± 1.9% above baseline. These data indicate that ONHBF starts to increase at levels of approx. 50% increase in OPP: This is slightly lower than the values we previously reported from LDF data. Signals from the PPR may have input from both, the retina and the choroid, but the relative contribution is unknown. In addition, retinal BF appears to increase at slightly lower OPP values of approximately 45%. LSFG may be used to study ONH autoregulation in diseases such as glaucoma.