Platelet Proteome Reveals Novel Targets for Hypercoagulation in Pseudoexfoliation Syndrome.

Pseudoexfoliation syndrome (PEX) is characterized by the accumulation of abnormal extracellular matrix material in ocular and non-ocular tissues, including blood vessel walls. Clot-forming dysfunction might be responsible for venous thrombosis in PEX. We investigated global coagulation, the proteome, and functions of platelets in PEX patients and aimed to determine prognostic biomarkers for thrombosis risk in PEX. Peripheral blood was collected from PEX and retinal vein occlusion (RVO) patients, and age-sex matched controls. Viscoelastic hemostasis was evaluated by rotational thromboelastometry (ROTEM). Platelet markers (CD41, CD42, CD61, and CD62p) and endothelial markers (P-selectin, E-selectin, and von Willebrand factor) were investigated by flow cytometry and ELISA, respectively. The platelet proteome was analyzed by 2D fluorescence difference gel electrophoresis followed by mass spectrometry. Clot formation time (CFT) is significantly reduced in PEX patients compared to the controls (p < 0.05). P-selectin levels were higher in PEX patients than in controls (p < 0.05); E-selectin and von Willebrand factor remained unchanged. The monitorization of CFT by ROTEM, and soluble P-selectin, may help assess thrombotic risk in PEX patients. Proteomic analysis revealed differential expression of Profilin-1 in platelets. Profilin-1 regulates the stability of actin-cytoskeleton and may contribute to impaired platelet hemostatic functions. Increased P-selectin levels together with impaired coagulation dynamics might be responsible for the thrombotic events in PEX disease.

HENLE FIBER LAYER MAPPING WITH DIRECTIONAL OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To perform a macular volumetric and topographic analysis of Henle fiber layer (HFL) from retinal scans acquired by directional optical coherence tomography. METHODS: Thirty healthy eyes of 17 subjects were imaged using the Heidelberg spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering, Heidelberg, Germany) with varied horizontal and vertical pupil entry. Manual segmentation of HFL was performed from retinal sections of horizontally and vertically tilted optical coherence tomography images acquired within macular 20 × 20° area. Total HFL volume, mean HFL thickness, and HFL coverage area within Early Treatment for Diabetic Retinopathy Study grid were calculated from mapped images. RESULTS: Henle fiber layer of 30 eyes were imaged, segmented and mapped. The mean total HFL volume was 0.74 ± 0.08 mm 3 with 0.16 ± 0.02 mm 3 , 0.18 ± 0.03 mm 3 , 0.17 ± 0.02 mm 3 , and 0.19 ± 0.03 mm 3 for superior, temporal, inferior, and nasal quadrants, respectively. The mean HFL thickness was 26.5 ± 2.9 µ m. Central 1-mm macular zone had the highest mean HFL thickness with 51.0 ± 7.6 µ m. The HFL coverage that have thickness equal or above to the mean value had a mean 10.771 ± 0.574 mm 2 of surface area. CONCLUSION: Henle fiber layer mapping is a promising tool for structural analysis of HFL. Identifying a normative data of HFL morphology will allow further studies to investigate HFL involvement in various ocular and systemic disorders.

REPEATABILITY OF CHOROIDAL VASCULARITY INDEX MEASUREMENTS USING DIRECTIONAL OPTICAL COHERENCE TOMOGRAPHY IMAGES.

PURPOSE: To investigate the repeatability of choroidal vascularity index (CVI) measurements in centered and decentered (regarding pupil entry position of the beam) directional subfoveal optical coherence tomography (OCT) scans with (CVI1) and without (CVI2) brightness adjustment. METHODS: Thirty-two eyes of 32 healthy volunteers were included in this prospective study. First, the fovea was evaluated by a single horizontal enhanced depth imaging OCT scan in a centered direction. Then, the same subfoveal horizontal line was scanned in a decentered direction. The agreement between CVIs obtained from these centered and decentered directional OCT scans was investigated using Bland-Altman analysis and intraclass correlation coefficient. RESULTS: Intraclass correlation coefficient between centered and decentered CVI1 was 0.71 (95% CI: 0.48-0.85, P value < 0.001). Intraclass correlation coefficient between centered and decentered CVI2 was 0.73 (95% CI: 0.5-0.86, P value < 0.001). The mean difference between centered and decentered directional measurements for CVI1 and CVI2 were 0.5 and 0.8, respectively. CONCLUSION: There is moderate agreement between CVIs obtained from centered and decentered directional single OCT scans of the same subfoveal area. Studies investigating choroidal vascularity should be standardized by using the same OCT beam direction in all scans.

Analysis of the Peripapillary Choroidal Vascular Characteristics in Papilledema Associated with Pseudotumor Cerebri.

SIGNIFICANCE: Choroidal vascularity index measured by image binarization method from peripapillary optical coherence tomography sections has been found significantly lower in papilledema patients than healthy controls. PURPOSE: The purpose of this study was to compare peripapillary choroidal parameters in papilledema patients with control subjects. METHODS: Peripapillary spectral domain optical coherence tomography scans of 34 patients with papilledema and 34 healthy controls are acquired for the study. Images are binarized with the ImageJ software (National Institutes of Health, Bethesda, MD) to calculate total choroidal area, stromal area, luminal area, and choroidal vascularity index. RESULTS: Total choroidal area, luminal area, and choroidal vascularity were significantly lower in papilledema patients compared with healthy controls on right (1.343 ± 0.286 vs. 1.694 ± 0.344, P < .001; 0.880 ± 0.209 vs. 1.167 ± 0.255, P < .001; 65.28 ± 2.99% vs. 68.68 ± 2.81%, P < .001, respectively) and left eyes (1.376 ± 0.308 vs. 1.647 ± 0.339, P < .001; 0.899 ± 0.231 vs. 1.134 ± 0.237, P < .001; 64.92 ± 3.44 vs. 68.84 ± 3.23, P < .001, respectively). No difference was found between active and remitted stages of papilledema in terms of choroidal parameters. CONCLUSIONS: Peripapillary total choroidal area, luminal area, and choroidal vascularity index are significantly reduced in patients with papilledema. These parameters might be beneficial tools for evaluating choroidal vascularity in papilledema quantitatively and differential diagnosis for optic disc edema.

Swabs Containing Tea Tree Oil and Chamomile Oil Versus Baby Shampoo in Patients With Seborrheic Blepharitis: A Double-Blind Randomized Clinical Trial.

PURPOSE: The comparison of the efficacy of swabs containing tea tree oil and chamomile oil and baby shampoo (BS) in the treatment of seborrheic blepharitis was aimed. METHODS: This randomized, double-blind, parallel-group, active control, multicenter clinical trial included patients with seborrheic blepharitis using block randomization (BS, n=23; swabs, n=26). Patients were treated with BS or swabs for 8 weeks followed by 4 weeks of treatment withdrawal. Change in Blepharitis Symptom measure (BLISS), Demodex count, Ocular Surface Disease Index (OSDI) score, Schirmer test, tear breakup time (TBUT), noninvasive TBUT (NI-TBUT), corneal staining, and meibography at different visits (baseline, fourth, , and 12th week) were the main outcome measures. RESULTS: Patients in both groups showed similar baseline parameters (P>0.05). Patients using swabs showed significantly lower BLISS scores compared with patients using BS at the 4th, 8th, and 12th week visits (3.6±6.1 vs. 6.3±4.5 P=0.011; 1.1±2.8 vs. 6.6±6.7, P<0.001; 0.9±2.8 vs. 5.7±6.6, P=0.002, respectively). Patients using swabs showed improvement in OSDI scores after 8 weeks of treatment compared with the baseline visit (P<0.001). Despite a similar Demodex reduction effect in both treatment arms even after 4 weeks of treatment (P<0.001), both treatment modalities did not show any effect on the other parameters. CONCLUSION: Although both swabs and BS showed efficacy for the treatment of seborrheic blepharitis in terms of the Demodex reduction and symptomatic improvement, swabs may provide better symptomatic improvement. Four weeks of treatment discontinuation may not cause any recurrence in the symptoms or Demodex infestation.

Choroidal vascularity index in pseudoexfoliative glaucoma.

PURPOSE: To evaluate choroidal vascular involvement in pseudoexfoliative glaucoma (PEXG) by applying the choroidal vascularity index (CVI) to optic coherence tomography (OCT) images. METHODS: Seventy-eight eyes from 40 subjects were included the study. Group 1 included healthy eyes (n = 20), group 2 eyes with PEX (n = 16), and group 3 eyes with PEXG (n = 42). OCT imaging of macular and peripapillary regions and retinal nerve fiber layer (RNFL) analyses were performed. CVI was calculated using ImageJ software. RESULTS: The mean age was 64.89 ± 5.8, 71.2 ± 7.8, and 68.24 ± 7.4 years in groups 1, 2, and 3, respectively (p = 0.046). There were no significant differences between the groups in terms of sex (p = 0.777). In macula, mean CVI rates were 66.97 ± 1.9%, 64.23 ± 1.2%, and 64.63 ± 1.6%, and in the peripapillary areas, mean CVI rates were 67.04 ± 1.5%, 65.20 ± 1.5%, and 64.14 ± 2.1% in groups 1, 2, and 3, respectively (group 1 vs. group 2 and 3, p = 0.000; group 2 vs. group 3, p > 0.05). The decrease in average RNFL thickness was statistically significant in group 3 compared to groups 1 and 2. CONCLUSION: CVI could be used to assess choroidal vascular changes in ocular diseases. CVI was found to be reduced in PEX and PEXG, indicating an ocular vascular involvement in pseudoexfoliative process.

Biocompatible Quantum Funnels for Neural Photostimulation.

Neural photostimulation has high potential to understand the working principles of complex neural networks and develop novel therapeutic methods for neurological disorders. A key issue in the light-induced cell stimulation is the efficient conversion of light to bioelectrical stimuli. In photosynthetic systems developed in millions of years by nature, the absorbed energy by the photoabsorbers is transported via nonradiative energy transfer to the reaction centers. Inspired by these systems, neural interfaces based on biocompatible quantum funnels are developed that direct the photogenerated charge carriers toward the bionanojunction for effective photostimulation. Funnels are constructed with indium-based rainbow quantum dots that are assembled in a graded energy profile. Implementation of a quantum funnel enhances the generated photoelectrochemical current 215% per unit absorbance in comparison with ungraded energy profile in a wireless and free-standing mode and facilitates optical neuromodulation of a single cell. This study indicates that the control of charge transport at nanoscale can lead to unconventional and effective neural interfaces.

Meibomian Gland Dysfunction in Primary and Secondary Sjögren Syndrome.

PURPOSE: We hypothesized that women with primary (pSS) and secondary Sjögren syndrome (sSS; with systemic lupus erythematosus [SLE] or rheumatoid arthritis [RA]) have meibomian gland dysfunction (MGD). We sought to test our hypothesis. METHODS: Subjects with pSS, sSS + SLE, sSS + RA, and non-SS-related MGD were recruited from the Sjögren's Syndrome Foundation or outpatient clinics at Tufts University School of Dental Medicine or Brigham and Women's Hospital. The control population was recruited from the Greater Boston area. After providing written informed consent, the subjects underwent an eye examination and/or completed two questionnaires that assess symptoms of dry eye disease (DED). RESULTS: Our results demonstrate that pSS and sSS patients have MGD. These subjects had meibomian gland orifice metaplasia, an increased number of occluded meibomian gland orifices, and a reduced quality of meibomian gland secretions. Further, patients with pSS, sSS + SLE, sSS + RA, and MGD had significant alterations in their tear film, lid margin, cornea, and conjunctiva. Symptoms of DED were increased ∼10-fold in all pSS, sSS, and MGD groups relative to controls. CONCLUSIONS: Our findings support our hypothesis and show that individuals with pSS, sSS + SLE, and sSS + RA have MGD. In addition, our study indicates that patients with pSS and sSS have both aqueous-deficient and evaporative DED.

Capacitive and Efficient Near-Infrared Stimulation of Neurons via an Ultrathin AgBiS2 Nanocrystal Layer.

Colloidal nanocrystals (NCs) exhibit significant potential for photovoltaic bioelectronic interfaces because of their solution processability, tunable energy levels, and inorganic nature, lending them chemical stability. Silver bismuth sulfide (AgBiS2) NCs, free from toxic heavy-metal elements (e.g., Cd, Hg, and Pb), particularly offer an exceptional absorption coefficient exceeding 105 cm-1 in the near-infrared (NIR), surpassing many of their inorganic counterparts. Here, we integrated an ultrathin (24 nm) AgBiS2 NC layer into a water-stable photovoltaic bioelectronic device architecture that showed a high capacitive photocurrent of 2.3 mA·cm-2 in artificial cerebrospinal fluid (aCSF) and ionic charges over 10 µC·cm-2 at a low NIR intensity of 0.5 mW·mm-2. The device without encapsulation showed a halftime of 12.5 years under passive accelerated aging test and did not show any toxicity on neurons. Furthermore, patch-clamp electrophysiology on primary hippocampal neurons under whole-cell configuration revealed that the device elicited neuron firing at intensity levels more than an order of magnitude below the established ocular safety limits. These findings point to the potential of AgBiS2 NCs for photovoltaic retinal prostheses.

Molecular detection of lacrimal apparatus and ocular surface - related ABC transporter genes.

The ocular system is in constant interaction with the environment and with numerous pathogens. The ATP-binding cassette (ABC) transporters represent one of the largest groups among the transmembrane proteins. Their relevance has been demonstrated for their defense function against biotic and abiotic stress factors, for metabolic processes in tumors and for their importance in the development of resistance to drugs. The aim of this study was to analyze which ABC transporters are expressed at the ocular surface and in the human lacrimal apparatus. Using RT-PCR, all ABC transporters known to date in humans were examined in tissue samples from human cornea, conjunctiva, meibomian glands and lacrimal glands. The RT-PCR analyses revealed the presence of all ABC transporters in the samples examined, although the results for some of the 48 transporters known in human and analyzed were different in the various tissues. The present results provide information on the expression of ABC transporters at the mRNA level on the ocular surface and in the lacrimal system. Their detection forms the basis for follow-up studies at the protein level, which will provide more information about their physiological significance at the ocular surface and in the lacrimal system and which may explain pathological effects such as drug resistance.

Ocular surface changes in mice with streptozotocin-induced diabetes and diabetic polyneuropathy.

PURPOSE: Diabetes mellitus (DM) is a leading risk factor for corneal neuropathy and dry eye disease (DED). Another common consequence of DM is diabetic peripheral polyneuropathy (DPN). Both complications affect around 50 % of the DM patients but the relationship between DM, DED and DPN remains unclear. METHODS: In this study, we examined mice with early onset of DM and PN after streptozotocin (STZ)-induced diabetes (DPN). We compared the early morphological changes of the sciatic nerve, dorsal root and trigeminal ganglia with the changes in the ocular surface, including tear proteomic and we also investigated respective changes in the gene expressions and morphological alterations in the eye tissues involved in tear production. RESULTS: The lacrimal gland, conjunctival goblet cells and cornea showed morphological changes along with alterations in tear proteins without any obvious signs of ocular surface inflammation. The gene expression for respectively altered tear proteins i.e., of Clusterin in cornea, Car6, Adh3a1, and Eef1a1 in eyelids, and Pigr in the lacrimal gland also showed significant changes compared to control mice. In the trigeminal ganglia like in the dorsal root ganglia neuronal cells showed swollen mitochondria and, in the latter, there was a significant increase of NADPH oxidases and MMP9 suggestive of oxidative and neuronal stress. In the dorsal root ganglia and the sciatic nerve, there was an upregulation of a number of pro-inflammatory cytokines and pain-mediating chemokines. CONCLUSION: The early ocular changes in DM Mice only affect the lacrimal gland. Which, is reflected in the tear film composition of DPN mice. Due to the high protein concentration in tear fluid in humans, proteomic analysis in addition to noninvasive investigation of goblet cells and cornea can serve as a tools for the early diagnosis of DPN, DED in clinical practice. Early treatment could delay or even prevent the ocular complications of DM such as DED and PN.

A first-in-human pilot study of a novel electrically-passive metamaterial-inspired resonator-based ocular sensor embedded contact lens monitoring intraocular pressure fluctuations.

Glaucoma is a leading cause of blindness with no cure, but early treatment and effective monitoring can often slow the progression of the disease. Monitoring of glaucoma is based on the measurement of intra-ocular pressure (IOP) that is a physiological parameter related to the mechanical state and parameters of the eye. Conventionally, diagnosing and assessing the progression of glaucoma is based on the method of measuring IOP discretely at clinics. Recent studies have demonstrated the importance of continuously monitoring IOP for 24 h to elucidate the effect of circadian rhythm. In this work, a metamaterial-inspired electrically-passive sensor-embedded contact lens is presented to monitor the IOP fluctuations based on a first-in-human pilot study. The sensor inside the contact lens is an electrically passive, metamaterial-based resonator that can be measured using a wearable antenna patch. The system has been tested with six healthy volunteers during an experiment to induce deliberate IOP changes via water-loading and placing the individuals in supine position using a recliner seat. The initial data compared with tonometer measurements suggest that the system can be used to assess the variation of IOP continuously.

In Vivo Confocal Microscopy Findings After Anterior Stromal Puncture in the Treatment of Recurrent Corneal Erosion Syndrome.

Objectives: The objectives of the study are to show up the healing processes after anterior stromal puncture (ASP) in the cornea using in vivo confocal microscopy (IVCM) and to investigate the efficacy of ASP in the treatment of recurrent corneal erosion (RCE). Methods: This is a prospective, non-randomized, consecutive series. Twenty-three eyes of 19 patients diagnosed with RCE were evaluated between March 2020 and January 2022. Outcome measures included age, sex, laterality, etiology of RCE, duration and recurrence of symptoms, additional treatments required, and complications. IVCM was performed on the same day, at 1st week, 1st, and 6th month. Results: Mean age was 41.5±11.3 years, 63.2% of patients were female and 65.2% of eyes had unilateral involvement. Corneal trauma (56.5%) was the most common cause. Mean follow-up was 21.1 months (range 8-33). At the final follow-up, 69.5% of eyes were symptom free, 17.4% required a second ASP, and 13% needed a third ASP. At the 1st week, the epithelium became intact. An increase in activated keratocytes and dendritic cells (DCs) with beading of nerve fibers was observed. At 1st month, DCs and activated keratocytes were still present. At the 6th month, a scar was left. The superficial and basal epithelial cell formation and subbasal corneal nerve plexus returned to normal. Conclusion: IVCM has a superiority in visualizing cornea at cellular level. After ASP which is a safe, practical, and cost-effective treatment option in paracentral or peripherally located RCE, IVCM may help the surgeon to better observe and understand the post-healing processes and explain the recurrences.

Retinal neurodegeneration in metabolic syndrome: a spectral optical coherence tomography study.

AIM: To evaluate the effects of metabolic syndrome (MetS) on retinal neurodegeneration by optical coherence tomography (OCT). METHODS: Patients diagnosed as MetS were compared with the age and sex-matched healthy control group (CG). Waist circumference measurements, fasting serological biochemical tests, and systemic blood pressures of all participants were evaluated. The MetS group was divided into 3 subgroups according to the number of MetS components: hypertension, diabetes mellitus, dyslipidemia (low-, high-density lipoprotein, hypertriglyceridemia), and visceral obesity findings; 3-component MetS3, 4-component MetS4, and all-component MetS5. All patients underwent complete eye examination and spectral OCT retinal imaging. RESULTS: Totally 58 eyes of 58 patients were included in the MetS group and 63 eyes of 63 age and sex-matched healthy subjects were included in CG. MetS group was composed of 22 subjects in MetS3, 21 subjects in MetS4, and 15 subjects in the MetS5 subgroup. Mean foveal thickness (MetS, 218.7±23.1 µm vs CG, 228.8±21.9 µm, P=0.015), mean inferior (MetS, 283.4±17.0 µm vs CG, 288.7±38.4 µm, P=0.002), superior (MetS, 287.0±18.5 µm vs CG 297.3±17.1 µm, P=0.001), nasal (MetS 287.3±16.7 µm vs CG 297.9±13.9 µm, P=0.000) and temporal (274.5±17.6 µm vs CG 285.6±13.6 µm, P=0.000) thickness in the 3 mm Early Treatment of Diabetic Retinopathy Study (ETDRS) circle was significantly lower in the MetS group. There was no statistically significant difference in the mean inferior, superior, nasal, and temporal thickness of 6 mm ETDRS circle, total macular volume, peripapillary and macular retinal nerve fiber layer, macular ganglion cell layer with inner plexiform layer, and ganglion cell complex. No statistically significant difference was found in these values ​​between the MetS3, MetS4, and the MetS5 groups. CONCLUSION: A significant reduction in central macular region thickness in MetS is detected and macular thickness is more susceptible to MetS induced neurodegeneration than peripapillary retinal nerve fiber layer.

Dynamic accommodation measurement using Purkinje reflections and machine learning.

Quantifying eye movement is important for diagnosing various neurological and ocular diseases as well as AR/VR displays. We developed a simple setup for real-time dynamic gaze tracking and accommodation measurements based on Purkinje reflections, which are the reflections from front and back surfaces of the cornea and the eye lens. We used an accurate eye model in ZEMAX to simulate the Purkinje reflection positions at different focus distances of the eye, which matched the experimental data. A neural network was trained to simultaneously predict vergence and accommodation using data collected from 9 subjects. We demonstrated that the use of Purkinje reflection coordinates in machine learning resulted in precise estimation. The proposed system accurately predicted the accommodation with an accuracy better than 0.22 D using subject's own data and 0.40 D using other subjects' data with two-point calibration in tests performed with 9 subjects in our setup.

Comparison of surgically induced astigmatic changes after cataract surgery in post-Laser in situ keratomileusis corneas versus virgin eyes.

PURPOSE: Postoperative refraction in modern mi-croincision cataract surgery gained extra importance in patients with the previous laser-assisted in situ keratomileusis (LASIK) surgery. The surgically induced astigmatic changes in those eyes may differ not only in magnitude but also in direction compared to virgin corneas. This study aimed to compare the surgically induced astigmatic changes after microscopic cataract surgery between post-LASIK corneas and virgin eyes. METHODS: Cases that underwent microincision cataract surgery in eyes with and without previous LASIK surgery were reviewed. The demographics, the axial length at cataract surgery, the central corneal thickness, spheric and cylindric values, keratometry readings, and postoperative posterior corneal astigmatism were retrospectively evaluated. A modified Alpins method was used for astigmatic vector analysis, and baseline astigmatism, surgically induced astigmatism, difference vector, flattening effect, and torque were assessed. RESULTS: A total of 42 eyes from 24 subjects was evaluated. Group I consisted of 14 eyes with the previous LASIK, and Group II included 28 eyes without any refractive surgery. Preoperative mean central corneal thickness in Group I was significantly thinner (p=0.012). There was no significant difference in baseline astigmatism between the groups regarding magnitude and power vectors. After microincision cataract surgery, there were no significant differences in mean spheric and cylindric values and mean keratometry readings (all p>0.05). However, surgically induced astigmatism and difference vector were significantly higher on J45 vector component in post-LASIK eyes and microincision cataract surgery steepening effect on post-LASIK corneas was significantly higher than those in virgin eyes (p=0.001, p=0.002 and p=0.018, respectively). CONCLUSIONS: Cataract surgery has steepened the corneas in both groups with a significantly higher steepening effect in post-LASIK eyes. Certainly, corneal topography cataract surgery is particularly helpful to provide more precise surgically induced astigmatism interpretations.

TFOS lifestyle: Impact of societal challenges on the ocular surface.

Societal factors associated with ocular surface diseases were mapped using a framework to characterize the relationship between the individual, their health and environment. The impact of the COVID-19 pandemic and mitigating factors on ocular surface diseases were considered in a systematic review. Age and sex effects were generally well-characterized for inflammatory, infectious, autoimmune and trauma-related conditions. Sex and gender, through biological, socio-economic, and cultural factors impact the prevalence and severity of disease, access to, and use of, care. Genetic factors, race, smoking and co-morbidities are generally well characterized, with interdependencies with geographical, employment and socioeconomic factors. Living and working conditions include employment, education, water and sanitation, poverty and socioeconomic class. Employment type and hobbies are associated with eye trauma and burns. Regional, global socio-economic, cultural and environmental conditions, include remoteness, geography, seasonality, availability of and access to services. Violence associated with war, acid attacks and domestic violence are associated with traumatic injuries. The impacts of conflict, pandemic and climate are exacerbated by decreased food security, access to health services and workers. Digital technology can impact diseases through physical and mental health effects and access to health information and services. The COVID-19 pandemic and related mitigating strategies are mostly associated with an increased risk of developing new or worsening existing ocular surface diseases. Societal factors impact the type and severity of ocular surface diseases, although there is considerable interdependence between factors. The overlay of the digital environment, natural disasters, conflict and the pandemic have modified access to services in some regions.

Cellular changes of the corneal epithelium and stroma in herpes simplex keratitis: an in vivo confocal microscopy study.

PURPOSE: To analyze the morphologic features of corneal epithelial cells and keratocytes by in vivo confocal microscopy in patients with herpes simplex keratitis (HSK) as associated with corneal innervation. DESIGN: Prospective, cross-sectional, controlled, single-center study. PARTICIPANTS: Thirty-one eyes with the diagnosis HSK and their contralateral clinically unaffected eyes were studied and compared with normal controls (n = 15). METHODS: In vivo confocal microscopy (Confoscan 4; Nidek Technologies, Gamagori, Japan) and corneal esthesiometry (Cochet-Bonnet; Luneau Ophthalmologie, Chartres, France) of the central cornea were performed bilaterally in all patients and controls. Patients were grouped into normal (>5.5 cm), mild (>2.5-5.5 cm), and severe (<2.5 cm) loss of sensation. MAIN OUTCOME MEASURES: Changes in morphologic features and density of the superficial and basal epithelial cells, as well as stromal keratocytes, were assessed by 2 masked observers. Changes were correlated to corneal sensation, number of nerves, and total length of nerves. RESULTS: There was a significant and gradual decrease in the density of superficial epithelial cells in HSK eyes, with 852.50 ± 24.4 cells/mm(2) in eyes with severe sensation loss and 2435.23 ± 224.3 cells/mm(2) in control eyes (P = 0.008). Superficial epithelial cell size was 2.5-fold larger in HSK eyes (835.3 µm(2)) compared with contralateral or normal eyes (407.4 µm(2); P = 0.003). A significant number of hyperreflective desquamating superficial epithelial cells were present in HSK eyes with normal (6.4%), mild (29.1%), and severe (52.2%) loss of sensation, but were absent in controls. The density of basal epithelial cells, anterior keratocytes, and posterior keratocytes did not show statistical significance between patients and controls. Changes in superficial epithelial cell density and morphologic features correlated strongly with total nerve length, number, and corneal sensation. Scans of contralateral eyes did not show any significant epithelial or stromal changes compared with controls. CONCLUSIONS: In vivo confocal microscopy reveals profound HSK-induced changes in the superficial epithelium, as demonstrated by increase in cell size, decrease in cell density, and squamous metaplasia. This study demonstrated that these changes correlate strongly with changes in corneal innervation.

Clinically relevant biometry.

PURPOSE OF REVIEW: Obtaining precise postoperative target refraction is of utmost importance in today's modern cataract and refractive surgery. Given the growing number of patients undergoing premium intraocular lens (IOL) implantations, patient expectation continues to rise. In order to meet heightened patient expectations, it is crucial to pay utmost attention to patient selection, accurate keratometry and biometry readings, as well as to the application of correct IOL power formula with optimized lens constants. This article reviews recent advances in the field of clinical biometry and IOL power calculations. RECENT FINDINGS: Recently developed low-coherence reflectometry optical biometry is comparable to older ultrasonic biometric and keratometric techniques. In addition, the new IOLMaster software upgrade has improved reproducibility and enhanced signal acquisition. Further, the modern lens power formulas currently determine the effective lens position and the shape of the intraocular lens power prediction curve more accurately. SUMMARY: In order to reach target refraction, precise biometric measurements are imperative. Understanding the strengths and limitations of the currently available biometry devices allows prevention of high variability and inaccuracy, ultimately determining the refractive outcomes.

Astigmatic Vectorial Analysis in Pediatric Keratoconus After Unilateral Cross-Linking Treatment.

PURPOSE: The aims of this study were to evaluate the treatment response of pediatric keratoconus (KC) patients to unilateral corneal collagen cross-linking (CXL) in treated eyes, disease progression in untreated eyes, and define the predictive value of astigmatic parameters by astigmatic vectorial analysis. METHODS: Pediatric patients with KC with CXL-treated progressive eye and untreated fellow eye were included. Patients with other ocular conditions and a history of previous ocular surgery were excluded. Astigmatic changes in anterior and posterior corneal surfaces were evaluated with vectorial analysis. The receiver operating characteristic curves were analyzed to detect the best parameter that discriminates treated and untreated groups. RESULTS: Thirty-two eyes of 16 patients with at least 2-year follow-up were analyzed. The maximum keratometry (K) in CXL-treated eyes remained stable (from 53.51 ± 2.86-53.41 ± 2.84 diopter (D), P = 0.84) while the steepest K increased in untreated eyes (from 47.82 ± 1.71-49.59 ± 3.32 D, P = 0.03). The oblique components of corneal astigmatism in CXL-treated eyes were higher than those of fellow eyes (all P < 0.05), which significantly decreased in the anterior 3-mm zone after treatment (P = 0.048). The mean differential astigmatism magnitudes were significantly higher in treated eyes (all P < 0.05). The refractive centroid remained unchanged in treated eyes (P = 0.553) and shifted in the oblique direction in untreated eyes (P = 0.04). The oblique differential astigmatism in the anterior 7-mm zone showed the highest area under the curve value in predicting treatment efficacy (0.813, 95% confidence interval: 0.646-0.981, P < 0.001). CONCLUSIONS: Astigmatic vectorial analysis is an objective tool for longitudinal assessment of clinical outcomes in KC. Changes in the oblique components of corneal astigmatism might predict progression and treatment efficacy.