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Purpose: To report a case of a Henle fiber layer hemorrhage as the initial manifestation of Factor V Leiden disease., Methods: Case report and literature review., Results: A healthy 19-year-old patient presented with a spontaneous Henle fiber layer (HFL) hemorrhage. The genetic analysis showed a previously unknown homozygous Factor V Leiden Mutation. No specific treatment was given due to the patient's good visual acuity and favorable prognosis, but the diagnosis of a Factor V Leiden mutation enabled a correct therapeutic management to be followed by the patient., Conclusion: Advances in eye imaging allow to detect ocular findings that may lead to an early diagnosis and treatment. To the best of our knowledge, this is the first case of a HFL hemorrhage as the initial manifestation of Factor V Leiden disease. Further research is needed to identify the pathways linking these findings., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To review the prevalence and describe the characteristics, of cases with late-onset intracorneal ring segments (ICRS) keratopathy in a multicenter study., Methods: A retrospective multicentric case-series study was performed in a specialized keratoconus service, from Buenos Aires, Argentina. An electronic clinical chart from patients with ICRS keratopathy between January 1999 and January 2019 was reviewed. We included cases with late-onset distal-apical ICRS keratopathy, which was defined as a persistent corneal lesion developed 12 months or later after implantation, located over, around, or closer to the ICRS. All the surgeries were performed by a manual corneal tunnel creation technique. Samples were taken to rule out infectious etiology., Results: From 5217 eyes that underwent ICRS implantation, 13 cases (0.24%) were detected. The keratopathy onset was 72 ± 42.98 months (29-133) after ICRS implantation. Cultures were negative in all cases. An ICRS exchange was made for five cases in stage I and four in stage II. Four cases presented with partial ICRS extrusion in stage III. ICRS exchange was possible in two of them and a penetration keratoplasty was necessary for the rest. All cases remained stable 1 year after surgical procedures., Conclusions: A late-onset distal-apical ICRS keratopathy was detected with low prevalence (0.24%) in a large sample. It was classified into three stages according to its severity. Different treatments were selected for each stage, obtaining stable results 1 year after treatment., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

In the field of Ophthalmology, the mNGS 16S rRNA sequencing method of studying the microbiota and ocular microbiome is gaining more and more weight in the scientific community. This study aims to characterize the ocular microbiota of patients diagnosed with keratoconus who have not undergone any prior surgical treatment using the mNGS 16S rRNA sequencing method. Samples of naïve keratoconus patients were collected with an eNAT with 1 mL of Liquid Amies Medium (Copan Brescia, Italy), and DNA was extracted and analyzed with 16S NGS. The microbiota analysis showed a relative abundance of microorganisms at the phylum level in each sample collected from 38 patients with KC and 167 healthy controls. A comparison between healthy control and keratoconus samples identified two genera unique to keratoconus, Pelomonas and Ralstonia. Our findings suggest that alterations in the microbiota may play a role in the complex scenario of KC development.

Introduction: The success of keratoplasty strongly depends on the health status of the transplanted endothelial cells. Donor corneal tissues are routinely screened for endothelial damage before shipment; however, surgical teams have currently no means of assessing the overall viability of corneal endothelium immediately prior to transplantation. The aim of this study is to validate a preoperative method of evaluating the endothelial health of donor corneal tissues, to assess the proportion of tissues deemed suitable for transplantation by the surgeons and to prospectively record the clinical outcomes of a cohort of patients undergoing keratoplasty in relation to preoperatively defined endothelial viability., Methods and Analysis: In this multicentre cohort study, consecutive patients undergoing keratoplasty (perforating keratoplasty, Descemet stripping automated endothelial keratoplasty (DSAEK), ultra-thin DSAEK (UT-DSAEK) or Descemet membrane endothelial keratoplasty) will be enrolled and followed-up for 1 year. Before transplantation, the endothelial viability of the donor corneal tissue will be evaluated preoperatively through trypan blue staining and custom image analysis to estimate the overall percentage of trypan blue-positive areas (TBPAs), a proxy of endothelial damage. Functional and structural outcomes at the end of the follow-up will be correlated with preoperatively assessed TBPA values., Ethics and Dissemination: The protocol will be reviewed by the ethical committees of participating centres, with the sponsor centre issuing the final definitive approval. The results will be disseminated on ClinicalTrials.gov, at national and international conferences, by partner patient groups and in open access, peer-reviewed journals., Trial Registration Number: NCT05847387., Competing Interests: Competing interests: YZ, SK and VR are editors of BMJ Open Ophthalmology., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

During infectious keratitis, the production of collagenolytic and inflammatory substances, along with increased corneal matrix metalloproteinase (MMP) activity, induces the degradation of corneal collagen and may cause postkeratitis complications, such as opacity, thinning, and corneal perforation. MMPs, especially MMP-2 and MMP-9, are overexpressed in infectious keratitis and sustained over time by inflammatory and nonmicrobial mechanisms. The high MMP levels are correlated with excessive corneal destruction in bacterial, herpetic, fungal, and acanthamoeba infections. Nonspecific treatments, such as tetracyclines, particularly doxycycline, or corticosteroids, are used as adjuvants to antimicrobials to alleviate the disproportionate degradation and inflammation of the corneal layers caused by corneal MMPs and decrease the recruitment and infiltration of inflammatory cells. Treatments showing inhibition of specific MMPs (Galardin, ZHAWOC7726), interfering with pro-MMP activation (EDTA, ascorbic acid), or showing anticytokine effect (epigallocatechin-2-gallate, TRAM-34) have been reported. Other treatments show a direct action over corneal collagen structure such as corneal cross-linking or have been associated with reduction of MMP levels such as amniotic membrane grafting. Although the use of these drugs has been shown in studies to be effective in controlling inflammation, especially in experimental ones, robust studies are still needed based on randomized and randomized clinical trials to demonstrate their potential effect as adjuvants in the management of infectious keratitis., Competing Interests: Declaration of Competing Interest The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the cut-off points for age and metrics provided by cataract grading objective systems for which a reestablishment in contrast sensitivity (CS) is expected after multifocal intraocular lens (MIOL) implantation., Methods: One hundred seven subjects were included in this retrospective analysis carried out during the screening for presbyopia and cataract surgery. Monocular distance corrected contrast sensitivity defocus curve (CSDC) and visual acuity were measured, and crystalline lens sclerosis was graded with three objective metrics: Ocular Scatter Index (OSI), Dysfunctional Lens Index (DLI) and Pentacam Nucleus Staging (PNS). A CS value of 0.8 logCS at far distance, following published literature on this matter, was selected to compute the cut-off that maximized the detection of eyes exceeding this value at the preoperative screening, either for age or objective metrics., Results: The CDCS showed a stronger correlation than CDVA with objective grading methods, whereas all objective metrics were significantly correlated between them (p < 0.05). The cut-offs for age, OSI, DLI and PNS were ≤ 62, ≤ 1.25, ≥ 7.67 and ≤ 1, respectively. The OSI provided the highest area under the receiver operating characteristic curve (0.85) followed by the age (0.84), DLI (0.74) and PNS (0.63)., Conclusions: Surgeons conducting clear lens exchange should communicate the possible distance CS loss after surgery with MIOL implantation according to the previous described cut-offs points. Age in combination with any cataract grading objective system is recommended to detect possible inconsistencies., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: This study conducted a critical review of the peer-reviewed literature on the use of supplemental toric intraocular lenses (STIOL) in the ciliary sulcus to correct residual refractive astigmatism., Methods: This review used PubMed as a database from 1 January 2010 to 13 March 2023. According to the inclusion and exclusion criteria defined, 14 articles were selected for the current review., Results: The data of 155 eyes were analyzed. Most of the studies reviewed had a short follow-up and poor or limited design, including case reports, case series, and retrospective cohorts. The follow-up period ranged from 43 days to 4.5 years. STIOL rotation was the most frequently described complication in the literature, with a mean rotation of 30.48 ± 19.90°. These patients required repositioning in 50 of 155 eyes (32.25%). Moreover, four eyes (2.58%) required scleral fixation sutures and two eyes (1.29%) iris fixation. Other complications were high intraocular pressure (3 eyes, 1.93%), transient corneal edema (2 eyes, 1.29%), corneal decompensation (2 eyes, 1.29%), and pigment dispersion (1 eye, 0.64%). From the total, 57.41% of eyes (89 eyes from 155) achieved within ± 0.50D of target refractive astigmatism. It is important to highlight that at least 52 eyes out of the 155 (33.54%) had an abnormal cornea with irregular astigmatism., Conclusion: STIOL seem to offer good visual and refractive outcomes. However, STIOL showed variable rotational stability, especially in some platforms. Further studies with a more robust design, methodology, and standardized analysis methods are needed to confirm these trends., (© 2023. The Author(s).)

Purpose: To assess how eye axes and multifocal intraocular lens (MIOL) centration may impact the light distortion index (LDI) and ocular scatter index (OSI)., Methods: Fifty-eight subjects implanted with the trifocal MIOL Q-Flex M 640PM or Liberty 677MY (Medicontur) were included in this retrospective analysis. The following variables were collected with the Pentacam Wave (Oculus) considering the vertex normal as the coordinates center: chord-mu to the center of the pupil, chord-alpha to the geometrical center of the cornea, and chord-MIOL to the center of the diffractive ring. These measurements were correlated with OSI (HD Analyzer, Visiometrics) and LDI (light distortion analyzer, CEORLab)., Results: Chord-MIOL centroid was 0.12 mm at 62°, chord-mu was 0.09 mm at 174°, and chord-alpha was 0.38 mm at 188°. A relationship was found between OSI and LDI, rho = 0.58, p < 0.0005). No relationships were found between chord-mu or chord-alpha and the LDI or OSI, neither for the total magnitude, nor the decomposition in orthogonal components (p > 0.05). The LDI was significantly correlated with the temporal centration of the MIOL versus the vertex normal (rho = 0.32, p = 0.02)., Conclusions: As opposed to what has been previously described, the temporal centration of the MIOL was related to a decrease in the LDI. Future studies with extreme values of the included variables are required to establish cut-offs for considering these variables as exclusion criteria in the implantation of a MIOL., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To evaluate the efficacy and safety of contact lenses (CL) as a therapeutic option for patients affected by a corneal disease and to determinate which is the best lens modality for each disease., Methods: A literature review using PubMed was performed. All relevant articles published during the last 15 years have been included., Results: Various studies point to CL as the best therapeutic option for some corneal diseases and even as an alternative to surgery in some cases. After fitting, patients show an improvement in their functional vision and quality of life, in some cases being able to drive or work again., Conclusions: There is a lack of scientific evidence to determine which lens modality is suitable for each corneal pathology. Currently, according to this review, the reason for choosing between the different options depends on the severity of symptoms, and it is worth mentioning that scleral lenses seem to be the best option in advanced stages of disease. However, the expertise of professionals is also an important factor at the time of choosing a particular CL modality. Standardized criteria are still necessary for correct selection of lens modality for a correct management of the disease., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Contact Lens Association of Ophthalmologists.)

Several clinical techniques have been described to evaluate visual performance and optical quality with intraocular lenses (IOL). However, subjective refraction remains one of the most important methods for assessing post-surgery results, taking decisions about retreatments, advanced spectacle prescription and the refinement of the constant for the formula used in the IOL power calculation. Beyond clinical refraction, defocus curve measurement has been described as a complementary tool for assessing visual performance and taking clinical decisions. However, to date, there are no clinical guidelines or evidence-based protocols published in the scientific literature recommended for pseudophakic patients implanted with either monofocal or multifocal IOLs. This narrative review highlights the importance of clinical refraction in pseudophakic eyes, its utility in the decision of different types of IOL implantation, and describes a clinical refraction protocol for eyes implanted with monofocal and multifocal IOLs., Competing Interests: Declaration of Competing Interests Authors have nothing to disclose., (Copyright © 2023 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: To evaluate the microbiota of culture negative Corneal Impression Membrane (CIM) microbial keratitis samples with the use of shotgun metagenomics analysis., Methods: DNA of microbial keratitis samples were collected with CIM and extracted using the MasterPure™ Complete DNA and RNA Purification Kit (Epicentre). DNA was fragmented by sonication into fragments of 300 to 400 base pairs (bp) using Bioruptor® (Diagenode, Belgium) and then used as a template for library preparation. DNA libraries were sequenced on Illumina® HiSeq2500. The resulting reads were quality controlled, trimmed and mapped against the human reference genome. The unmapped reads were taxonomically classified using the Kraken software., Results: 18 microbial keratitis samples were included in the study. Brevundimonas diminuta was found in 5 samples while 6 samples showed the presence of viral infections. Cutibacterium acnes , Staphylococcus aureus , Moraxella lacunata and Pseudomonas alcaligenes were also identified as the presumed putative cause of the infection in 7 samples., Conclusions: Shotgun sequencing can be used as a diagnostic tool in microbial keratitis samples. This diagnostic method expands the available tests to diagnose eye infections and could be clinically significant in culture negative samples.

Cataract surgery has become a refractive procedure in which emmetropia is the goal, with the implantation of extended depth-of-focus or multifocal intraocular lenses (IOLs) being the commonly selected option to restore vision beyond the far distance. The selection criteria for implanting these lenses can differ from those for monofocal IOLs and even between technologies, as eye characteristics can affect postoperative visual performance. Corneal astigmatism is an eye characteristic that can affect visual performance differently, depending on the implanted IOL. The magnitude of corneal astigmatism, the tolerance of the IOL to this astigmatism, economic aspects, comorbidities, and the efficacy of astigmatism treatment are factors that can make surgeons' doubt as to what astigmatism treatment should be applied to each patient. This review aims to summarize the current evidence related to low astigmatism tolerance in presbyopia-correcting lenses, the efficacy achieved through corneal incisions, and their comparison with the implantation of toric IOLs., (© 2023. The Author(s).)

A new technique that allows implanting intracorneal ring-segments (ICRS) from the limbal zone is described. Using a femtosecond laser (FSL), a 360° corneal tunnel is created with an internal diameter of 5.4 mm and an external diameter of 7.0 mm, with a wider area (0.2 mm inner and 0.2 mm outer) in the upper 60° of the tunnel (called landing zone). Next, a 4.36 mm-long corneal-limbal incision was created with the FSL, which connects to the bubbles created in the landing zone. The entire procedure was performed using intraoperative optical coherence tomography (OCT). Once the two incisions were connected using blunt-edged Mac Pherson forceps, the bubbles were released from the surgical plane. The programmed ICRS(s), 6 mm in diameter, are then placed in the corneal tunnel from the limbal incision with the aid of Sinskey forceps. Finally, when the ICRS is in place, the surgery is complete., Competing Interests: The authors declare no conflicts of interest.

The purpose of this study was to evaluate the agreement between three methods for measuring pupil size in patients implanted with multifocal intraocular lenses (MIOLs): Keratograph 5M (K5M), Pentacam AXL Wave (PW), and a simple hand ruler. Sixty-nine subjects implanted with MIOLs and measured at the three-month follow-up visit were included in this retrospective analysis. K5M and PW were used to measure the photopic (PP) and mesopic (MP) pupil sizes, and a hand ruler was used to measure the pupil under environmental light conditions (135 lux). The Bland-Altman method with its limits (LoAs) was used to assess the agreement. The median PP was 2.8, 2.95, and 3 mm for K5M, PW, and the ruler, respectively ( p < 0.05). Differences in PP were statistically significant for all paired comparisons ( p < 0.0005) except between PW and the ruler ( p = 0.44). The LoAs for the difference in PP between K5M and PW was 0.63 mm. The mean difference for MP between K5M and PW was 0.04 mm ( p = 0.34) with LoAs of 0.72 mm. MP measured with K5M and PW could be considered interchangeable, although a correction of -0.3 mm (IC95%: -0.23 to -0.39) should be applied to PP measured with PW to attain the K5M mean.

There are currently two authorized vaccines against herpes zoster (HZ) that have been shown to be safe and effective in its prevention: Zostavax, a zoster vaccine live (ZVL), and Shingrix, a recombinant zoster Vaccine (RZV). Because ophthalmologists work with vision-threatening complications of zoster, such as herpes zoster ophthalmicus (HZO), they are in a good position to advocate for vaccination. Our aim was to determine the current knowledge among Spanish ophthalmologists about the effectiveness of the available vaccines against HZ. A Google Forms questionnaire was created and used as the survey platform for this study. It was an anonymous online survey of 16 questions, which was shared among Spanish ophthalmologists in-training and consultants from 27 April 2022 to 25 May 2022. The survey was completed by a total of 206 ophthalmologists of all subspecialties. We obtained responses from 17 of the 19 regions of Spain. Fifty-five percent of the respondents agreed that HZ is a frequent cause of vision loss. However, 27% of the professionals were unaware of the existence of vaccines against HZ and 71% of them did not know in which cases it could be indicated. Only nine ophthalmologists (4%) had ever suggested vaccination against HZ to their patients. Despite this, 93% considered it important to recommend vaccination against HZ if it proved to be safe and effective. Considering the sequelae, complications, and the existence of safe and effective vaccines against HZ, vaccination of the target population could be considered an important public health measure. We are convinced that it is time for ophthalmologists to take an active role in HZO prevention.

Aim: To evaluate the effectiveness of pars plana vitrectomy (PPV) without macular intervention on uveitis eyes with persistent vitreous inflammation/opacities in terms of visual acuity (VA), intraocular inflammation and macular profile., Methods: We carried out a single-center retrospective study of patients with uveitic eyes that underwent PPV without intervention on the macula due to persistent vitreous inflammation/opacities. The primary outcome measures were best-corrected visual acuity (BCVA), intraocular inflammation and macular profile at 3, 12 and 24 months after surgery., Results: Twenty-seven eyes of twenty-six patients were analyzed. Overall, 77.8% had an improvement of VA (55% by 0.3 LogMAR or more); 62.5% of patients had no intraocular inflammation, and the number of patients on systemic steroids and second-line immunosuppressives was reduced by 26% at 12 months; 87.5% of patients had resolution of macular oedema at 12 months., Conclusion: PPV for persistent vitreous inflammation/opacities is safe and effective, showing beneficial outcomes in terms of improvement of BCVA and the reduction in inflammation.

Introduction: The purpose of this article was to ascertain the existing literature and find the gaps in economic evaluations of cataracts., Methods: Systematic methods were used to search and collect the published literature on economic evaluations of cataracts. A mapping review of studies published in the following bibliographical databases was performed: the National Library of Medicine (PubMed), EMBASE, Web of Science (WOS), and the Central of Reviews and Dissemination (CRD) database. A descriptive analysis was conducted and relevant studies were classified into different groups., Results: Among 984 studies screened, 56 studies were included in the mapping review. Four research questions were answered. There has been a progressive increase of publications during the last decade. The majority of the included studies were published by authors from institutions in the USA and UK. The most commonly investigated area was cataract surgery followed by intraocular lenses (IOLs). The studies were classified into different categories according to the main outcome evaluated, such as comparisons between different surgical techniques, costs of the cataract surgery, second eye cataract surgery costs, quality of life gain after cataract surgery, waiting time of cataract surgery and costs, and cataract evaluation, follow-up, and costs. In the IOL classification, the most frequently studied area was the comparison between monofocal and multifocal IOLs, followed by the comparison between toric and monofocal IOLs., Conclusions: Cataract surgery is a cost-effective procedure compared with other non-ophthalmic and ophthalmic interventions and surgery waiting time is an important factor to consider because vision loss has a huge and broad-ranging impact on society. Numerous gaps and inconsistencies are found among the studies included. For this reason, there is a need for further studies according to the classification described in the mapping review., (© 2023. The Author(s).)

Suprachoroidal hemorrhage (SCH) is a rare and sight-threatening complication of various intraocular surgeries, including cataract surgery. Although the rate of SCH complicating cataract surgery has decreased in the era of phacoemulsification, most likely due to smaller self-sealing incisions and modern equipment, it remains a challenging complication to manage. The aim of this review is to summarize the current evidence of the pathophysiology and management of SCH complicating phaco surgery. A literature review was performed using the PubMed database searching for diagnosis, therapy, and management of SCH during phacoemulsification. The evidence available on the optimal management of this condition is low, and there is no consensus so far. An early diagnosis is thought to be essential to avoid progression to the devastating stage of expulsion of intraocular contents (expulsive hemorrhage). Sudden intraoperative anterior chamber shallowing, red reflex loss, and a significant increase in intraocular pressure are highly suspicious for this severe complication. A fundus examination and ocular ultrasound are crucial to confirm the diagnosis and, if it is confirmed, stabilize the globe immediately. The initial therapeutic approach includes aggressive topical and systemic medication focused on controlling ocular inflammation and intraocular pressure, whereas the timing and the indications of surgical intervention remain controversial., Competing Interests: The authors declare no conflict of interest.

Background: New intraocular lenses (IOLs) have emerged since the originally coined monofocal and multifocal IOLs. The extended depth of focus (EDoF) and enhanced monofocal IOLs (mono-EDoF) that have appeared in the last decade have caused some confusion in their classification. The aim of this review was to summarize the outcomes provided by mono-EDOF IOLs and to determine which of the endpoints, described by the American National Standard (ANSI) for EDoF IOLs, are fulfilled., Methods: The MEDLINE, EMBASE, and WEB OF SCIENCE databases were searched. Two independent reviewers screened the studies for inclusion and data extraction. The search strategy was limited to studies published between 2020 and 2022, but not by language. The results are presented as a narrative summary accompanied by tables, in alignment with the objectives of this scoping review. Compliance with the endpoints for clinical outcomes described in the American National Standard Z80.35-2018 (ANSI) for EDoF lenses was checked and additional endpoints were defined., Results: Two systematic reviews, 13 laboratory, 21 clinical, and two mixed studies were included. Tecnis Eyhance was the mono-EDOF with the highest volume of evidence to date. Although laboratory studies included other IOLs, clinical evidence for them is still scarce, with only one study of IsoPure compared to a standard monofocal IOL. Evidence in comparison to EDoF lenses is also scarce, even for Tecnis Eyhance, with only three studies including this lens in comparison to an EDoF lens. After evaluation of the ANSI criteria, agreement was found in the failure for the increase in depth of field equal to or greater than 0.5 D for a visual acuity (VA) level of 0.2 logMAR and none of the studies supported that the median monocular VA at intermediate distance was at least 0.2 logMAR., Conclusions: Additional clinical evidence is required for other mono-EDOF IOLs beyond Tecnis Eyhance. Until the arrival of a standard classification, mono-EDOF should be better still classified as monofocal because the ANSI standards were not fully met., (© 2023. The Author(s).)

The aim of this study was to collect the scientific literature on the correction of presbyopia with laser in situ keratomileusis (presbyLASIK) in last years and to analyse the quality of such scientific evidence using a validated methodology for conducting a systematic review. A total of 42 articles were initially identified, but after applying the selection criteria and an additional manual search a total of 23 articles were finally included: 2 non-randomized controlled clinical trials (NRCT) and 21 case series. Quality assessment of NRCTs and case series was performed with the ROBINS-I and the 20-criterion quality appraisal checklist defined by Moga et al. (IHE Publ 2012), respectively. For NRCT, the risk of bias was moderate in one study and serious in the other NRCT, being the main sources of risk, the domains related to confounding, selection of participants and measurement of outcomes. For case series studies, the main source of risk of bias was subjects not entering the study at the same point of the conditions (different levels of presbyopia). Likewise, a significant level of uncertainty was detected for the following items: consecutive recruitment of patients, blinding of outcome assessors to the intervention that the patient received, and conclusions of the study not supported by the results. Research on presbyLASIK to this date is mainly focused on case series generating a limited level of scientific evidence. The two NRCTs identified only demonstrated the potential benefit of combining the multiaspheric profile with some level of monovision in the non-dominant eye., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Descemet membrane endothelial keratoplasty (DMEK) is a popular procedure for the treatment of corneal endothelial diseases mainly targeting Fuchs endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK). Although DMEK has multiple advantages, it is challenging in terms of graft preparation and delivery. One of the crucial factors of DMEK graft preparation is determining the size of the graft. Evaluating risks and benefits of transplanting larger or smaller grafts compared with the descemetorhexis performed following a standard DMEK procedure thus becomes important. Advanced techniques like pre-loaded DMEK requires pre-selection of graft diameter without physical examination of the eye making it more challenging. Therefore, recognizing the benefits of graft size and the number of transplanted endothelial cells becomes essential. Smaller DMEK grafts have been preferred and accepted for grafting. Larger diameter grafts have advantages but can be challenging due to higher detachment rates. We thus aim to review the challenges of preparing and delivering DMEK tissues with small or large diameter based on selected descemetorhexis area, discuss the outcomes based on different graft sizes, highlight related complications and suggest which cases may benefit from adopting smaller or larger graft size., (© 2022 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Dry eye has two basic subdivisions: aqueous deficient dry eye (ADDE), with SS a major cause; and evaporative dry eye (EDE), due to either intrinsic or extrinsic factors. SS is a chronic inflammatory disorder defined by dysfunction of the exocrine glands leading to dry eye and dry mouth. The objective of this article was to carry out a systematic and critical review of several scientific publications on dry eye disease, with the aim of providing general recommendations to distinguish dry eye and its different variants in patients with SS, during the period 1979 to 2020, using search engines for articles indexed in Scopus, Latindex, Scielo, Clinical Trials, Medline, Embase, and Cochrane, allowing the analysis of 132 articles published in indexed journals on the subject of dry eye disease and SS, evidencing its conceptualization, prevalence, risk factors, etiopathogenesis, clinical manifestations, diagnosis, and treatment.

Purpose: To assess agreement between corneal aberration measurements made through swept-source optical coherence tomography using a new anterior segment imaging device (Anterion) and a Scheimpflug imaging device (Pentacam HR) in healthy subjects., Methods: Cross-sectional study. In 50 eyes of 50 healthy subjects, 14 aberration parameters (7 across the anterior corneal surface and 7 across the total surface) were measured in 4 mm and 6 mm optic zones using each device: oblique trefoil (Z3&#95;-3), vertical coma (Z3&#95;-1), horizontal coma (Z3&#95;1), horizontal trefoil (Z3&#95;3), spherical aberration (Z4&#95;0), root mean square (RMS) lower order aberrations (LOA) and RMS higher order aberrations (HOA). Data for the two devices were compared through intraclass correlation coefficients (ICC), paired t tests, limits of agreement (LoA) and Bland Altman plots., Results: Vertical coma was the only corneal aberration parameter that consistently showed excellent agreement (ICC > 0.8, mean difference -0.019, LoA -0.165 to 0.126). Good agreement (ICC = 0.75) between the devices was observed for RMS HOA, but this was slightly worse in the 6 mm optical zone (ICC = 0.667 for anterior RMS HOA). No over- or underestimation trend by one or other device was noted. Agreement was poor to moderate for the rest of the corneal parameters (ICC 0.2 to 0.7)., Conclusion: Despite good agreement overall for vertical coma and RMS HOA values, agreement for the remaining corneal aberration measurements was poor to moderate. As mean differences in our sample were overall small, in normal eyes these devices could be clinically judged as interchangeable.

Purpose: The aim of this study was to evaluate the feasibility of Descemet membrane endothelial keratoplasty (DMEK) tissue preparation using a glasses-assisted 3-dimensional (3D) display system and to compare it with a conventional surgical microscope., Methods: Healthy pairs of human corneas suitable for penetrating keratoplasty surgery were selected for this study. The tissues were randomly divided into 2 groups. Each pair of corneas had 1 cornea (group 1) prepared with NGENUITY (Alcon) with a 5-second staining time with vision blue, and the fellow cornea (group 2) was prepared using a OPMI Lumera 700 surgical microscope (Carl Zeiss Meditec, Jena, Germany) with a 30-second staining time. DMEK graft preparation time, speed of stripping, graft width, and endothelial cell loss were evaluated., Results: Twenty-eight pairs of corneas were included in this study. The graft preparation time was significantly higher in the 3D group than in the conventional group (498 ± 147 vs. 418 ± 85 seconds, P value = 0.031). The mean speed of stripping was 0.59 ± 0.081 mm/s in group 1 and 0.089 ± 0.005 mm/s in group 2 ( P value = 0.024). The mean endothelial cell density in group 1 and group 2 before tissue preparation was 2162 ± 115.21 and 2153 ± 122.45, respectively ( P value > 0.1). After tissue preparation, the endothelial cell density reduced to 1911 ± 150.72 in group 1 and 1998 ± 90.72 in group 2 ( P value = P value > 0.05). The graft width was 5.05 ± 0.71 mm in group 1 and 4.92 ± 0.23 mm in group 2 ( P value > 0.05)., Conclusions: DMEK tissue preparation with 3D display system NGENUITY is feasible with a slightly increased preparation time. The improved visualization allows a reduced staining time that could be beneficial for eye banks because it may reduce the toxic effect of staining colorants., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To report the effectiveness of the surgical procedure of the tarsoconjunctival flap (FTC) in patients with severe ocular surface impairment refractory to previous conventional treatments., Methods: A retrospective, noncomparative, consecutive case series., Results: Pillar tarsoconjunctival flap (PTCF) was performed in eight eyes of eight patients. Three patients had neurotrophic corneal ulcer (NCU), three had exposure keratopathy and two had corneal melting. Seven of them had satisfactory postoperative results, showing total corneal re-epithelialization that lasted throughout the postoperative follow-up (mean 10.33 ± 2.65 months [SD], range 6 to 12 months). Mean time for the re-epithelization was 11.28 ± 8.97 days [SD] (range 4 to 30 days)., Conclusion: This study suggest PTCF is a valid alternative to tarsorrhaphy in cases of persistent epithelial defect (PED) or NCU resistant to conventional treatments. Notwithstanding, prospective comparative trials comparing PTFC with conventional and/or novel therapies in PED or NCU are needed to corroborate these findings.

Competing Interests: The author has no conflict of interest to declare.

Purpose: This study aims to explore and characterize healthy eye microbiota., Methods: Healthy subjects older than 18 years were selected for this descriptive cross-sectional study. Samples were collected with an eSwab with 1 mL of Liquid Amies Medium (Copan Brescia, Italy). Following DNA extraction, libraries preparation, and amplification, PCR products were purified and end-repaired for barcode ligation. Libraries were pooled to a final concentration of 26 pM. Template preparation was performed with Ion Chef according to Ion 510, Ion 520, and Ion 530 Kit-Chef protocol. Sequencing of the amplicon libraries was carried out on a 520 or 530 chip using the Ion Torrent S5 system (Thermo Fisher; Waltham, MA, USA). Raw reads were analyzed with GAIA (v 2.02)., Results: Healthy eye microbiota is a low-diversity microbiome. The vast majority of the 137 analyzed samples were highly enriched with Staphylococcus , whereas only in a few of them, other genera such as Bacillus, Pseudomonas, and Corynebacterium predominate. We found an average of 88 genera with an average Shannon index of 0.65., Conclusion: We identified nine different ECSTs. A better understanding of healthy eye microbiota has the potential to improve disease diagnosis and personalized regimens to promote health.

Small-aperture corneal inlays, commonly known as KAMRA, are tiny optical devices inserted in the corneal stroma aiming to gain near vision in patients with presbyopia. The purpose of this study was to systematically review case series of small-aperture corneal inlays performed in presbyopic emmetropic patients and to evaluate the visual outcomes of this procedure. This systematic review included 18 articles published between 2011 and 2018, overall studying 2724 eyes from 2691 participants. The mean longest follow-up was 19 months. Results showed that 78.5% of eyes reported an uncorrected near visual acuity of 20/32 or better and 90.50% of eyes achieved an uncorrected distance visual acuity of 20/25 or better. All patients experienced an improvement in uncorrected near visual acuity with a patient satisfaction ranging between 60% and 90%. The highlighted complications were keratocyte activation leading to corneal stromal haze, epithelial growth, iron deposits and poor distance visual acuity. Explantation was carried out in 101 eyes (3.7%) due to distance vision blurriness, development of epithelial microcysts, incorrect implant placement or hyperopic shift changes. KAMRA demonstrated high efficacy. However, safety and satisfaction rates remain unclear. Despite the low explantation rates reported in the literature, some complications were permanent. The results and conclusions should be taken with caution due to the conflict of interest stated in the reviewed articles., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

The aim of this study is to describe the involvement of Epstein-Barr Virus (EBV) in the diseases of the ocular anterior segment. This is a narrative review designed using the PUBMED, SCOPE and Web of Science databases, searching for reported literature on findings in the anterior ocular segment related to EBV between 1990 and 2020. Epstein-Barr Virus (EBV) is implicated in the development of salmon-coloured conjunctival masses in the context of acute mononucleosis and lymphoproliferative disorders. Moreover, EBV can cause haemorrhagic conjunctivitis and its corneal implications appear as different types of keratitis patterns. The involvement of EBV in the pathogenesis of anterior segment inflammation is not well-defined. Current evidence regarding anterior segment disease caused by EBV infection has been proved by positive viral detection through polymerase chain reaction test in eyes with lymphoproliferative disorders known to be caused by EBV, as B- and NK/T-cell lymphoid tumours. Antiviral treatment (oral Aciclovir or Valaciclovir) in anterior segment disease caused by EBV remains controversial., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To describe a new algorithm to measure corneal densitometry based on images obtained by swept source anterior segment ocular coherence tomography (SS-AS-OCT) and establish standard densitometry values in a group of normal eyes., Methods: A total of 111 healthy participants (195 eyes) were enrolled in this study. Using a MATLAB designed algorithm, the cornea was segmented into three layers: anterior, posterior and mid-stroma, and it was divided into two concentric areas, 0-2 and 2-4 mm, resulting in nine areas for the analysis. The mean corneal densitometry values were calculated and expressed as grayscale units (GSU)., Results: The mean age was 57 years (range 22-87), with 100 (51.3%) right eyes and 95 (48.7%) left eyes. The total corneal densitometry was 86.9 ± 12.1 GSU. The mid-stroma layer had the highest densitometry values, 87.4 ± 12.1 GSU, and the anterior layer had the lowest values, 81.9 ± 14.2 GSU. Densitometry differences between the anterior layer and the mid-stroma layer (P < 0.001), as well as the anterior layer and the posterior layer (P < 0.05) were statistically significant. The 0-2 mm concentric area had higher mean densitometry values, 97.8 ± 12.7 GSU, and the differences were significant compared to the 2-4 mm concentric area (P < 0.001). No correlation was found between the corneal densitometry values and gender or age., Conclusions: The new MATLAB segmentation algorithm for the analysis of corneal SS-AS-OCT images is capable to objectively assess corneal densitometry. We provide standard and normal data for better clinical and research approach., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Pseudopterygium is a non-progressive conjunctival adhesion to the peripheral cornea secondary to a corneal-limbus damage. According to the literature, the main etiology is a previous eye trauma. Nevertheless, this could be biased by the existence of other underdiagnosed causes of pseudopterygium, some of which may have severe consequences for the integrity of the eye and patient's life. This comprehensive literature review was performed based on a search on the PubMed and Google Scholar databases of relevant pseudopterygium published papers according to our current knowledge and seeks to gather the existing evidence about its diverse etiologies and clinical features, as well as to propose a diagnostic algorithm to simplify its correct approach.

This review discusses the role of opioids in the corneal surface and the different pathways and therapeutic methods of management. A literature review was performed using PubMed database. For the database search, the main searching words "opioid" and "topical opioid treatment" were used with the descriptors "cornea", "ocular surface", "neuropathic corneal pain", "corneal sensitivity" and "naltrexone"; original scientific articles and reviews were included to achieve the purpose of the review. The endogenous opioid system has relevant functions in the organism, and in daily use, opioids are used as painkillers. However, these drugs may be employed for other indications as opioid pathways have a wide spectrum. The corneal surface for topical treatment is easily accessible, hence sparing the side effects of systemic opioids. Instillation of opioid antagonist substances, such as naltrexone, increases corneal healing rates and stimulates the division of corneal epithelium cells without deleterious effects. The natural modulation of endogenous opioids controls different forms of pain, including inflammatory and neuropathic pain, both in the ocular surface and in the central nervous system. There are diverse methods in controlling pain using opioids, especially in refractory forms. This review attempts to collect the literature about corneal surface and opioid pathways to provide an overview image and a possible direction of the news treatments.

Purpose: To measure the effects of Autologous serum (AS), Allogeneic Serum (HS) and Umbilical Cord serum (CS) eye drops in severe dry eye disease (DES), as well as to characterize and quantify several molecules in the three sera (albumin, fibronectin; Vitamin A and E; IgG, IgA and IgM; Transforming growth factor β; Epithelial growth factor)., Methods: Randomized, double-blind, single-centre, three-arm (AS, HS and CS) clinical trial. Sixty-three subjects were included with severe DES, 21 in each arm of the study. Visual acuity, Schirmer test, Breakup time (BUT), lissamine green, fluorescein staining measurements and a questionnaire were performed prior to treatment, and after one-month and three-month follow-up., Results: There was a significant main effect of time on visual acuities, Schirmer and BUT tests and fluorescein and lissamine green staining measurements and questionnaire scores (p = 0.015, p = 0.002, p < 0.001, p < 0.001, p = 0.031 and p < 0.001, respectively), although there was no significant interaction between time and serum type, nor between serum type and the test performed. Regarding the concentration of molecules, in our study AS contained significantly higher concentrations of IgA, IgG and fibronectin whereas HS contained significantly higher concentration of IgM, vitamins A and E, TGF and albumin. Contrary to previous reports, CS did not show higher concentration of any of the molecules analysed., Conclusions and Relevance: The three sera were effective in the treatment of severe DES. CS did not contain a higher proportion of molecules compared to AS/HS. More research is needed to assess the effect of AS in patients with DES and autoimmune diseases., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To analyze astigmatism axis changes after tropicamide and phenylephrine combined instillation., Method: One hundred and thirty-one eyes from 66 patients enrolled this cross-sectional study. An extensive ocular examination was carried out prior to tropicamide and phenylephrine instillation. Power and axis value from flat, steep, and mean keratometry were calculated using an Auto Kerato-Refractometer (AKR). Later, topography and tomography maps were evaluated with Pentacam HR® (Oculus, Wetzlar, Germany). Subsequently, a single drop of tropicamide 1% and phenylephrine hydrochloride 10% were instilled twice, with a five-minute gap between each instillation. After 30 minutes, the AKR and Pentacam HR® tests were repeated., Results: Incyclotorsion was found in 59 eyes (45.1%) and mean absolute incyclotorsion change was 3.91 ± 3.62 degrees (0.10 to 14.20). Excyclotorsion was found in 72 eyes (54.9%) and mean excyclotorsion change was 4.99 ± 5.94 degrees (0.20 to 36.20). We observed that 74.6% and 68.1% of eyes experienced incyclotorsion and excyclotorsion within 0 to 5 degrees, respectively. Fewer patients experienced incyclotorsion and excyclotorsion changes within 5 to 10 degrees, precisely 11.8% and 19.4%, respectively. Eyes that experienced over 10 degrees of incyclotorsion and excyclotorsion were 13.6% and 12.5%, respectively., Conclusion: Astigmatism axis could change after combined tropicamide and phenylephrine instillation. Reference axis marking in astigmatism correction surgery should be performed under the same circumstances as the astigmatism axis has been measured.

Orbital inflammatory disease (OID), commonly known as orbital pseudotumour, is an inflammatory disease of unknown cause. It has different forms of presentation and different degrees of severity. Its variable nature is the main cause for this disease to be misdiagnosed and misclassified. The prognosis of OID depends on the tissues affected and the histology. OID usually responds favourably to systemic steroid treatment. However, empiric steroids may mask other underlying diseases that respond well to this treatment as well, namely, IgG4-related disease or lymphoproliferative disorders. This fact has led to controversy among various authors as some recommend performing a biopsy in most of the cases, whereas others defend that this procedure should only be performed if the patient has not responded to empiric steroid treatment. Although steroids have been the mainstream treatment of OID, the side effects, relapse rates and lack of response in some cases have resulted in them being replaced by immunosuppressive and immunomodulator therapies that currently stand as a key steroid-sparing treatment option, in addition to radiotherapy and surgery. The aim of this review is to update the evidence on the diagnosis and treatment of OID., (Copyright © 2021 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: To assess the influence of reliability (repeatability and reproducibility) of eye parameter measurements on the prediction refraction by using the outcomes of nine optical biometers reported in the literature., Methods: A search was conducted in PubMed focused on the outcomes from original studies regarding reliability. The mean population of within-subject standard deviation (Sw) was estimated from the mean samples reported in the included studies. Repeatability coefficients ( R ) for the mean population were computed as 2.77 × Sw. The influence of reliability on the prediction refraction for eye biometric parameters, such as mean corneal power in diopters (D) (Km), anterior chamber depth (ACD), and axial length (AXL), were evaluated using a thick lens formula. The lens thickness (LT), central corneal thickness (CCT), and white-to-white (WTW) distance were also evaluated., Results: The repeatability of optical biometers ranged from 0.19 to 0.42 D for Km, from 0.04 to 0.13 mm for ACD, from 0.03 to 0.22 mm for AXL, from 0.06 to 0.13 mm for LT, from 5.5 to 17.7 µm for CCT, and from 0.18 to 0.48 mm for WTW distance. Total prediction refraction due to repeatability ranged from 0.21 to 0.61 D, with Km the variable that caused the major part of total prediction refraction variability, followed by AXL and ACD. Reproducibility for the evaluated variables was generally inside the repeatability ranges., Conclusions: New optical biometers are equally reliable as earlier technologies. Special attention should be focused on Km and AXL, which explain the major part of prediction refraction variability. [ J Refract Surg . 2022;38(2):120-127.] .

Purpose: To review all case series of refractive corneal inlay implantation: Flexivue (Presbia, Netherlands), Invue (BioVision, Brügg, Switzerland) and Icolens (Neoptics, Hünenberg, Switzerland) performed in presbyopia patients and to evaluate the reported visual outcomes. In addition, our aim is to provide assessment for complications and to report the satisfaction rates., Methods: PubMed, Web of Science and Scopus databases were consulted using "refractive corneal inlay", "Flexivue Inlay", "Invue Inlay" and "Icolens inlay" as keywords. 147 articles were found, and they were assessed considering the inclusion and exclusion criteria. After filtering, this systemic review included ten articles, published between 2011 and 2020., Results: 308 eyes from 308 participants were enrolled in this systematic review. Mean maximum follow-up was 13.9 months. Nine of the ten case series included used femtosecond laser for the corneal pocket creation. Mean pocket depth was 293.75 µm. 77.5% of the eyes reported a postoperative uncorrected near visual acuity of 20/32 or better, and 19.20% of the inlay-implanted eyes achieved an uncorrected distance visual acuity of 20/20 or better. The most prominent complications were halos, pain, photophobia, and poor distance visual acuity. 27 eyes (8.7%) had to be explanted due to complications, such as near-distance spectacle dependence or blurred distance vision., Conclusion: Refractive corneal inlay outcomes demonstrated high efficacy, safety, and satisfaction rates. Furthermore, it is a reversible technique. However, the findings must be viewed with caution due potential conflict of interest. Further research with higher sample size is needed to validate these findings., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To evaluate the prediction error (PE) after applying the Abulafia-Koch formula in an online calculator with and without consideration of anterior corneal surgically induced astigmatism (SIA Cornea )., Methods: SIA Cornea models were calculated with a historical database of 204 right eyes (REs) from a single surgeon, either for manual (2.2 mm) or femtosecond (2.5 mm) temporal clear corneal incisions. PE was assessed in 58 REs operated by the same surgeon with a monofocal toric IOL and calculated, considering the PCA estimation in an online calculator with the combination of each one of the following SIA Cornea calculation approaches: (A) considering only significant centroids after stratification, (B) all centroids after stratification and (C) a single centroid without stratification., Results: The consideration of all centroids resulted in an underestimation of SIA Cornea in cases of preoperative against-the-rule astigmatism (ATR-A) and an overestimation in with-the-rule astigmatism (WTR-A). After stratification, SIA Cornea was only significant in preoperative ATR and oblique astigmatism cases for femtosecond incisions. PE considering PCA only was 0.03@160º. The combination with SIA Cornea resulted in a WTR-A surprise in preoperative ATR-A and WTR-A, however only being significant for preoperative ATR-A in calculation approaches B (0.29@84º) and C (0.21@80º). SIA Cornea addition to PCA estimation only reduced the centroid for oblique preoperative astigmatism., Conclusions: Surgeons should consider the calculation of the SIA Cornea after stratification by astigmatism type when using the same incision location (i.e. temporal). However, SIA Cornea derived from the anterior corneal surface should not be combined with PCA estimation for IOL power calculations.