Corneal Endothelial Damage Research Articles

Unexpected Intracameral Foreign Bodies During Regular Cataract Surgeries.

Unexpected intracameral foreign bodies during regular cataract surgery appear relatively often but seem to be underreported, since they are almost often immediately removed. They rarely remain in the anterior chamber and can be the source of inflammation, infections, or lead to corneal endothelial decompensation. We report two series of cases with different materials of different origins and review the literature. During several cases of uncomplicated phacoemulsifications under topical anesthesia, unknown foreign bodies visibly flushed in through the sleeve of the phaco handpiece. The material was always removed and submitted to the (Eidgenössische Materialprüfungs- und Forschungsanstalt; Federal Institute for Materials Testing and Research) for further investigations. Spectral analysis revealed that, in our cases, the foreign bodies were remnants of otherwise intact phaco sleeves that had not been cleaned properly during production. In another case series, the resin granules from the water filtration system for the instrument washing machine had found their way into the phaco handpieces. Many shapes and materials of different origins might unexpectedly appear during cataract surgery in the eye. Their immediate extraction is necessary, as they might cause corneal endothelial damage, chronic inflammation, or could be the source of infections. Vigilance reporting is also important for the controlling medicinal organizations and companies to assure early recognition of systematic problems.

A comparative study on the phaco time and corneal endothelial count in phacoemulsification using the stop & chop and divide & conquer techniques in Indian eyes

Cataract, a leading cause of curable blindness requires surgical management. Endothelium which is crucial for corneal transparency gets injured during intraocular surgeries like phacoemulsification. Various studies have compared the impact of different techniques of phacoemulsification on endothelium. But few studies conclude that Phaco time & endothelial loss is lesser in Stop & Chop than Divide & Conquer technique. An Interventional study involving 30 eyes in Group A (Stop & Chop) and 30 in Group B (Divide & Conquer) with Nuclear sclerosis grade II and III, excluding any pre-existing corneal diseases and Glaucoma was conducted in a tertiary care teaching hospital. All pre-operative parameters were similar in both groups. Post-operative values of best corrected visual acuity (BCVA), intra ocular pressure (IOP), endothelial cell count, central corneal thickness (CCT), Absolute Phaco time were recorded. Data entered in Excel sheets and analysed with SPSS. Paired, Unpaired t tests were used. P value <0.05 was statistically significant. Mean Absolute Phaco time for Group A was shorter (25.10±10.54 s) than that for Group B (44.20± 6.94 s) with statistical significance (p<0.05). Mean cell loss & changes in endothelium were higher in Group B than Group A (p<0.05). Absolute Phaco time was shorter in Stop & Chop than Divide & conquer as well as the corneal endothelial damage and changes were lesser in Group A. Hence Stop & Chop technique of phacoemulsification is recommended for less corneal morbidity.

Neuropeptide alpha-Melanocyte stimulating hormone preserves corneal endothelial morphology in a murine model of Fuchs dystrophy

Fuchs endothelial corneal dystrophy is a heterogenous disease with multifactorial etiology, and genetic, epigenetic, and exogenous factors contributing to its pathogenesis. DNA damage plays a significant role, with ultraviolet-A (UV-A) emerging as a key contributing factor. We investigate the potential application of neuropeptide α-melanocyte stimulating hormone (α-MSH) in mitigating oxidative stress induced endothelial damage. First, we examined the effects of α-MSH on a cultured human corneal endothelial cell line (HCEnC-21T) exposed to hydrogen peroxide (H2O2) induced oxidative DNA damage. We performed immunofluorescence and flow cytometry to assess DNA damage and cell death in the cultured cells. Additionally, we used an established mouse model that utilizes ultraviolet light to induce corneal endothelial cell damage resulting in decreased CEnC number, increased cell size variability, and decreased percentage of hexagonal cells. This endothelial decompensation leads to an increase in corneal thickness. Following UV-A exposure, the mice were systemically treated with α-MSH, either immediately after exposure (early treatment) or beginning two weeks post-exposure (delayed treatment). To evaluate treatment efficacy, we analyzed CEnC density and morphology using in vivo confocal microscopy, and central corneal thickness using anterior segment optical coherence tomography. Our findings demonstrated that α-MSH treatment effectively protects HCEnC-21T from free-radical induced oxidative DNA damage and subsequent cell death. In vivo, α-MSH treatment, mitigated the loss of CEnC density, deterioration of cell morphology and suppression of the resultant corneal swelling. These results underline the potential application of α-MSH as a therapeutic agent for mitigating corneal endothelial damage.

A Case of Irreversible Corneal Endothelial Damage Associated with Amantadine Use

Purpose: To report a case of irreversible corneal endothelial cell damage associated with amantadine administration.Case summary: A 60-year-old female patient was referred with bilateral painless corneal edema. There was no history of ocular trauma or surgery. The was no sign of ocular surface inflammation, such as, conjunctival injection, either. At presentation, her best corrected visual acuity (BCVA) was 20/100 in the right eye and 20/50 in the left eye. Review of the past medical history revealed that she had been diagnosed with Parkinson’s disease and had been taking amantadine (100 mg, twice a day) for 3 years. At 7 weeks after cessation of amantadine, corneal edema was resolved bilaterally and BCVA improved to 20/30 in the right eye and 20/20 in the left eye. However, specular microscopy showed low endothelial cell density (ECD) with 886 ± 297/mm2 in the right eye and 926 ± 374/mm2 in the left eye. At 4 months after cessation, there was no corneal edema and BCVA was 20/25 in the right eye and 20/20 in the left eye. However, ECD was low with 852 ± 249/mm2 in the right eye and 903 ± 332/mm2 in the left eye.Conclusions: In cases with bilateral corneal edema without no obvious pathology, the history of medication, such as, amantadine, should be reviewed. Although cessation of amantadine can lead to improvement of corneal edema, irreversible damage of the corneal endothelial cells may remain. Serial evaluation of corneal endothelial cells is therefore recommended in patients with systemic amantadine administration.

Particularities of Cataract Surgery in Elderly Patients: Corneal Structure and Endothelial Morphological Changes after Phacoemulsification.

The aim of this study was to evaluate the influence of ultrasounds used in phacoemulsification during cataract surgery on the corneal structure and morphology in patients over 65 years. We compared the outcomes of phacoemulsification techniques in terms of corneal cell morphology in 77 patients over 65 years old and 43 patients under 65 years old. Corneal cell density, central corneal thickness and hexagonality were measured preoperatively and post-surgery (at 1 and 4 weeks) by specular microscopy. The effect of gender, axial length and anterior chamber depth on the parameters of corneal endothelium were evaluated. In both groups, a progressive decrease in endothelial cells was observed, starting from the first week post-surgery until the fourth postoperative week. The central corneal thickness increased in both groups with maximum values at the first week postoperatively, while their initial values were restored in the fourth week post-surgery, with no statistical difference between groups. Statistically significant differences were noticed in terms of cell hexagonality in the group over 65, showing smaller hexagonality at all preoperative and postoperative time points compared to group under 65. Our result highlights the importance of routine specular microscopy performed before surgery, regardless the age of the patients, with caution and careful attention to the phaco power intensity, ultrasound energy consumption and intraoperative manipulation of instruments, as well as proper use of viscoelastic substances to reduce corneal endothelium damage, especially in elderly patients.

Direct Intraocular Lens Extraction Using a Newly Developed Lens-Grabbing Forceps.

Background: Due to lower age thresholds for cataract surgery and increased longevity, cases with intraocular lens (IOL) dislocation requiring removal have increased. Traditional methods, such as cutting or folding the IOL within the eye, pose a high risk of complications, including corneal endothelial and iris damage. Methods: We developed a new minimally invasive technique for direct IOL removal using specially designed lens-grabbing forceps. These forceps can grasp and remove the IOL through a small incision in a single motion, significantly reducing intraocular manipulations compared to conventional methods. Results: In our test cases, IOL removal through a 2.2 mm corneal incision was completed in approximately 95 s, with minimal incision enlargement (about 0.16 mm) and a slight decrease in corneal endothelial cells. Conclusions: Our findings suggest that this technique is minimally invasive and safe for IOL removal, offering a promising alternative to existing methods.

Statistical analysis plan for the phaco TIp position during clear corneal Phacoemulsification Surgery (TIPS) randomized controlled trial

BackgroundCornea is the most important refractive media in the eye, and damage to the corneal endothelium is one of the most common causes of poor visual outcome following cataract surgery, particularly in those with predisposing factors. The role of phaco tip position during phacoemulsification on corneal endothelial damage is ambiguous, and there is no consensus regarding the most cornea-friendly phaco tip position (bevel-up or bevel-down). The objective of the trial is to compare the effect of phaco tip position (bevel-up vs. bevel-down) during phacoemulsification using direct chop technique on corneal endothelial cell count.Methods and designTIPS is a randomised, multicentre, parallel-group, triple-masked (participant, outcome assessor, and statistician) trial with 1:1 allocation ratio. A total of 480 eligible participants, aged > 18 years with immature cataract, will be randomly allocated into bevel-up and bevel-down groups at two centres. Randomisation will be stratified according to the cataract grade. The primary outcome is postoperative endothelial cell count at 1 month. Secondary outcomes are central corneal thickness on postoperative days 1, 15, and 30 and difference in intraoperative complications.ConclusionIn this paper, we describe the detailed statistical analysis plan (SAP) for the TIPS trial, which was prepared prior to database lock. The SAP includes details of planned analyses and unpopulated tables, which will be reported in the publications. We plan to lock the database in July 2023 and publish the results later in the same year.SAP Version 0.1 (dated: 28 April 2023)Protocol version:2.0Trial registrationClinical Trial Registry of India CTRI/2019/02/017464. Registered on 5 February 2019; https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=29764&EncHid=&userName=2019/02/017464

Multiscale imaging of corneal endothelium damage and Rho-kinase inhibitor application in mouse models of acute ocular hypertension.

We developed a multiscale optical imaging workflow, integrating and correlating visible-light optical coherence tomography, confocal laser scanning microscopy, and single-molecule localization microscopy to investigate mouse cornea damage from the in-vivo tissue level to the nanoscopic single-molecule level. We used electron microscopy to validate the imaged nanoscopic structures. We imaged wild-type mice and mice with acute ocular hypertension and examined the effects of Rho-kinase inhibitor application. We defined four types of intercellular tight junction structures as healthy, compact, partially-distorted, and fully-distorted types by labeling the zonula occludens-1 protein in the corneal endothelial cell layer. We correlated the statistics of the four types of tight junction structures with cornea thickness and intraocular pressure. We found that the population of fully-distorted tight junctions correlated well with the level of corneal edema, and applying Rho-kinase inhibitor reduced the population of fully-distorted tight junctions under acute ocular hypertension. Together, these data point to the utility of multiscale optical imaging in revealing fundamental biology relevant to disease and therapeutics.

In‐vivo corneal collagen crosslinking using ruthenium and visible light

Aims/Purpose: Corneal collagen cross‐linking (CXL) treatment is widely applied to halt the progression of ectatic diseases such as keratoconus. Unfortunately, the standard CXL procedure based on riboflavin and UV‐A light can only be applied to cornea thicker than 400 μm and results in frequent complications, such as corneal haze and endothelial damage [1]. This study investigates a new CXL procedure based on ruthenium, which is a water‐soluble photoinitiator and visible light (430 nm) in vivo.Methods: For the CXL procedure, tris(bipyridine)ruthenium(II) ([Ru(bpy)3]2+), an SPS solution was applied to the rat's cornea and exposed to blue light. After the crosslinking procedure, observations were made for corneal opacity, corneal neovascularization, limbal neovascularization and corneal epithelial damage. Furthermore, the corneas were isolated for histopathological examination, cell viability and SEM analysis, and the results were compared with the conventional riboflavin/UV‐A crosslinking approach.Results: Crosslinked corneas with ruthenium‐based CXL approach showed significantly improved scoring in corneal opacity, corneal neovascularization, limbal neovascularization and corneal wound healing as compared to the standard riboflavin and UVA‐based CXL procedure. Histopathological analysis and cell viability revealed ruthenium to be nontoxic and create more bonds between collagen fibrils when observed under scanning electron microscopy.Conclusions: In this in vivo study, the ruthenium and visible light‐based crosslinking approach proved to be non‐toxic and a faster alternative to the conventional riboflavin and UVA‐based CXL method. We foresee that ruthenium visible light‐based crosslinking treatment could potentially change the treatment modality in keratoconus patients in a clinical setting.Funding Information: This work is supported by the Scientific and Technological Research Council of Turkey (TÜBİTAK) under GrantARDEB‐219S349.

Traumatic Anterior Dislocation of a Clear Crystalline Lens

We present a case study of a 41-year-old patient who was admitted to the ophthalmological emergency department complaining of ocular pain and redness following trauma of the right eye. Slit-lamp examination of the right eye revealed visual acuity limited to "counting fingers", diffuse conjunctival hyperemia, anterior dislocation of a clear crystalline lens in the anterior chamber with endothelial contact (Figure 1) , and ocular hypertonia measured at 35 mm Hg. Medical treatment was swiftly initiated, incorporating both local and systemic hypotensive agents. After the eye pressure has been normalized, the patient underwent phacoemulsification lens extraction with anterior vitrectomy. Postoperative outcome was marked by normalization of intraocular pressure and by the absence of optic nerve and corneal endothelial cell damage.

Conjunctival, Scleral and Corneal Complications in Vitreoretinal Surgery

Vitreoretinal surgery has been associated with corneal, conjunctival and scleral complications. These complications may cover corneal epithelial and endothelial cells damage (epithelial defects, neurotrophic and band keratopathy, refractive error changes, corneal decompansation etc.), ocular surface disease, early hypotonia, diplopia, strabismus, subconjunctival silicone oil, episcleral pigmentation, infection and inflammation etc. Risk factors may include a history of the previous ocular surgery, aphakia and pseudophakia, prolonged duration of surgery, intraoperative epithelial debridement, intraoperative lensectomy, diabetic patients, use of adjunctive intraocular long-acting expansile gases or silicone oil, use of scleral buckling, sutureless sclerotomy incisions etc. These complications should be known and noticed due to affect visual outcomes and healing of patients. Corneal, conjunctival and scleral complications are summarized in this article.

Adipose Mesenchymal Stem Cell-Derived Exosomes Promote the Regeneration of Corneal Endothelium Through Ameliorating Senescence.

Human corneal endothelial cells (hCECs) have been considered unable to regenerate in vivo, resulting in corneal decompensation after significant loss of hCECs. adipose-derived mesenchymal stem cell (ASC)-derived exosomes can regenerate tissues and organs. In this study, we investigated whether ASC-derived exosomes could protect and regenerate CECs. We performed cell viability and cell-cycle analyses to evaluate the effect of ASC-derived exosomes on the regeneration capacity of cultured hCECs. Transforming growth factor-β (TGF-β) and hydrogen peroxide (H2O2) were used to induce biological stress in CECs. The effect of ASC-derived exosomes on CECs was investigated in vivo. ASC-derived exosomes were introduced into rat CECs using electroporation, and rat corneas were injured using cryoinjury. Next-generation sequencing analysis was performed to compare the differentially expressed microRNAs (miRNAs) between ASC-derived and hCEC-derived exosomes. ASC-derived exosomes induced CEC proliferation and suppressed TGF-β- or H2O2-induced oxidative stress and senescence. ASC-derived exosomes protect hCECs against TGF-β- or H2O2-induced endothelial-mesenchymal transition and mitophagy. In an in vivo study, ASC-derived exosomes promoted wound healing of rat CECs and protected the corneal endothelium against cryoinjury-induced corneal endothelium damage. Next-generation sequencing analysis revealed differentially expressed miRNAs for ASC-derived and hCEC-derived exosomes. They are involved in lysine degradation, adherens junction, the TGF-β signaling pathway, the p53 signaling pathway, the Hippo signaling pathway, the forkhead box O (FoxO) signaling pathway, regulation of actin cytoskeleton, and RNA degradation based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. ASC-derived exosomes promoted wound healing and regeneration of endothelial cells by inducing a shift in the cell cycle and suppressing senescence and autophagy.

Endothelial dysfunction of the cornea after exposure to sprayed venom from hornets

Purpose Ocular injuries due to Hymenoptera venom are uncommon and most injuries occur on the ocular surface. We reported two rare cases of corneal endothelial damage caused by hornet venom that was sprayed, not injected, through stinging in the eye. Observations Case 1: A 57-year-old male patient was injured when a hornet sprayed venom into his left eye. He was referred to our hospital because the edoema and epithelial erosion of the cornea persisted. The patient presented with bullous keratopathy, asymmetrical iris atrophy, irreversible mydriasis, and glaucoma. His cataract progressed, and his best-corrected visual acuity was 0.03. Cataract surgery was performed after anti-inflammatory treatment with steroids, and Descemet-stripping automated endothelial keratoplasty was performed 6 months later. The patient recovered well postoperatively: his best-corrected visual acuity improved to 1.0 and he continued his glaucoma treatment. Case 2: A 75-year-old male patient had damage to his corneal epithelium, severe conjunctivitis, and conjunctival edoema when sprayed hornet venom entered his left eye. At initial presentation, the corneal endothelial cell density had decreased to 1042 cells/mm2. The conjunctival sac was washed, and steroid and topical antibacterial instillations were administered. His best-corrected visual acuity improved from 0.07 at the initial visit to 0.5. However, the corneal opacification and glaucoma persisted, and 3 months later the corneal endothelial cell density decreased to 846 cells/mm2. Conclusions and importance Corneal injuries caused by sprayed hornet venom are rare; however, they can cause intense anterior chamber inflammation and severe, irreversible corneal endothelial damage. In such cases, prompt initial treatment, the administration of adequate anti-inflammatory medication, and careful evaluation of the corneal endothelium are required.

Netarsudil-induced reticular epithelial oedema: An uncommon side effect

Netarsudil ophthalmic solution 0.02% (Netalo) is a new drug in the armamentarium for lowering intraocular pressure in open-angle glaucoma or ocular hypertension. It is a rho-associated protein kinase (ROCK) and norepinephrine transporter inhibitor with multiple mechanisms of action at various cellular levels. Apart from its effect on glaucoma, it has been reported to be beneficial in acute corneal endothelial damage. Its reported common side effects are conjunctival hyperaemia, corneal verticillata and subconjunctival haemorrhage. Corneal oedema arising from its use has been infrequently reported from abroad. We have presented two cases of such oedema acutely induced by Netarsudil, in the absence of any pre-existing corneal problems and which resolved on discontinuation. Such incidences warrant further studies to understand their clinical significance, the mechanism of corneal oedema arising from ROCK inhibitors and the use of these drugs in patients with compromised corneas.

Factors associated with severe corneal endothelial damage following acute primary angle closure in Chinese subjects

PurposeTo investigate the corneal endothelial damage caused by acute primary angle closure (APAC) and related risk factors for severe corneal endothelial cell damage in Chinese subjects.MethodsIn this multicentre retrospective study, 160 Chinese patients (171 eyes) diagnosed with APAC were recruited. Endothelial cell density (ECD) and morphological changes short after APAC were studied. Univariate regression and multivariate regression were used to identify risk factors associated with the extent of ECD reduction, including age, gender, education level, patients’ location, systemic diseases, APAC duration (hours), highest recorded intraocular pressure (IOP), and presenting IOP. Factors associated with the probability of severe corneal damage (ECD lower than 1000/mm2) were analysed based on a linear function.ResultsAfter one APAC episode, 12.28% eyes had ECD lower than 1000/mm2, 30.41% had ECD between 1000 and 2000/mm2, and 57.31% had ECD more than 2000/mm2. Attack duration was the only factor associated with severe endothelial damage (p < 0.0001). If the attack were to be subsided within 15.0 h, possibility of ECD lower than 1000/mm2 could be controlled under 1%.ConclusionShortly after the abortion of APAC, 12.28% patients experienced severe endothelial cell damage with ECD less than 1000/mm2. The only factor associated with severe ECD decrease was attack duration. Immediate and effective treatment is pivotal for preserving corneal endothelial function in APAC patients.

A Study of Corneal Endothelial Damage Following Different Type of Phacoemulsification Techniques

A Study of Corneal Endothelial Damage Following Different Type of Phacoemulsification Techniques

Evaluation of corneal endothelium and correlation with disease severity in patients with Graves’ ophthalmopathy: A specular microscopy-based study

PurposeTo investigate the possible corneal endothelial damage in Graves’ ophthalmopathy (GO) and its relationship with GO activity. MethodsThis cross-sectional study included 101 eyes of 55 patients with GO. Each eye was assigned a specific clinical activity score (CAS). Accordingly, they were classified as active (CAS ≥ 3) or inactive (CAS< 3). The corneal endothelium was measured using a non-contact specular microscope (Tomey EM-4000; Tomey Corp.). Endothelial cell density (ECD), average cell area (ACA), standard deviation of cell area (SD), coefficient of variation in cell area (CV), hexagonal cell ratio (HEX), and central corneal thickness (CCT) were recorded. ResultsAmong the eyes included in the study, 71 had inactive GO and 30 had active GO. ACA and HEX levels were lower (p<0,001) and CV values were higher (p<0.001) in patients with GO than in healthy subjects. Corneal endothelial cell morphology was altered in active GO compared to inactive GO. The SD (p = 0,009) and CV (p<0,001) were significantly higher in active GO than in inactive GO. When the parameters examined were correlated with CAS, a statistically significant positive correlation was observed between proptosis (p = 0,036, r = 0,385) and CV (p = 0,001, r = 0,595). ConclusionOur study confirmed that morphological changes occur in the corneal endothelium of patients with GO. CV and SD values, in conjunction with CAS, can be used as non-invasive and quantitative indices to examine the activity status of GO. The demonstration of endothelial changes even in GO eyes with low CAS may be considered an incentive to include non-contact specular microscopy in the routine clinical evaluation of all patients with GO.

Meta-analysis of corneal endothelial changes after phacoemulsification in diabetic and non-diabetic patients

BackgroundCurrently, there is still controversy about the differential changes in corneal endothelium function and morphology after phacoemulsification between Diabetes Mellitus (DM) and non-Diabetes Mellitus (non-DM) patients. In this study, we aimed to evaluate the influence of phacoemulsification on the corneal endothelium in DM and non-DM patients.MethodsDatabases of PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies published between January 1, 2011 and December 25, 2021. The weighted mean difference and 95% confidence interval were used to estimate the outcomes of statistical analyses performed.ResultsThirteen studies involving 1744 eyes were included in this meta-analysis. No significant difference was observed in the central corneal thickness (CCT), endothelial cell density (ECD), coefficients of variation (CV), or hexagonal cell percentage (HCP) between the DM and non-DM groups (CCT: P = 0.91; ECD: P = 0.07; CV: P = 0.06; HCP: P = 0.09) preoperatively. The CCT was significantly thicker in the DM group at 1 month (P = 0.003) and 3 months (P = 0.0009) postoperatively, and there was no significant difference at 6 months postoperatively (P = 0.26) than non-DM group. The CV was significantly higher and HCP was significantly lower in the DM group at 1 month (CV:P < 0.0001, HCP: P = 0.002), with no significant difference at 3 months (CV: P = 0.09, HCP: P = 0.36) and 6 months (CV: P = 0.32, HCP: P = 0.36) postoperatively than non-DM group. DM patients had lower ECD than non-DM patients at all postoperative time points (1 month, 3 months: P < 0.00001, 6 months: P < 0.0001).ConclusionsThe influence of phacoemulsification on corneal endothelial damage is greater in diabetic patients. Moreover, the recovery of corneal endothelial function and morphology is delayed in these patients. Clinicians should be more attentive to the corneal health of DM patients when considering phacoemulsification.

SRT1720 attenuates UVA-induced corneal endothelial damage via inhibition of oxidative stress and cellular apoptosis

Corneal endothelium is mostly sensitive to oxidative pressure and mitochondrial dysfunction. However, the oxidative-antioxidant mechanism of corneal endothelial cells (CECs) remains partially defined. Silent information regulator 1 (SIRT1) is a well-studied therapeutic target of oxidative damage. This study aimed to determine the SIRT1 expression in ultraviolet A (UVA)-induced corneal endothelial damage and explore potential drugs to repair corneal endothelial oxidative injury. In this study, we showed that CECs exhibited cellular apoptosis, reactive oxygen species (ROS) accumulation and decreased SIRT1 expression. In addition, UVA induced the imbalance of mitochondrial homeostasis and function, involving in mitochondrial membrane potential, mitochondrial fusion/fission and mitochondrial energy metabolism. SRT1720, the SIRT1 activator, effectively increased SIRT1 expression and attenuated UVA-induced oxidative damage in CECs. The therapeutic effects of SRT1720 for corneal endothelial oxidative damage were also verified in UVA-irradiated mice model. Our findings indicated that SIRT1 maintained the oxidant-antioxidant balance in corneal endothelium, suggesting a new promising therapeutic target for corneal endothelial dysfunction.

Does the phaco TIp position during clear corneal Phacoemulsification Surgery adversely affect corneal endothelium? TIPS study protocol for a randomised, triple-masked, parallel-group trial of bevel-up versus bevel-down phacoemulsification.

Introduction: Globally, at least 30 million cataract surgeries are required annually to prevent cataract-related blindness. Corneal endothelial decompensation is one of the most common causes of poor visual outcome following cataract surgery, particularly in those with predisposing factors. The increasing ageing population and reduced visual impairment threshold for cataract surgery have resulted in rising cataract surgical rates and hence, an increase in corneal endothelial decompensation is expected. The role of phaco tip position on corneal endothelial damage is ambiguous. Previous studies have reported contradictory results and were also underpowered to detect a significant difference due to small sample sizes. With no consensus regarding the most cornea-friendly phaco tip position (bevel-up versus bevel-down) during phacoemulsification, we propose a randomised clinical trial with a robust design using direct chop phaco-technique. Objective: To compare the effect of phaco tip position (bevel-up vs. bevel-down) on corneal endothelial cell count during phacoemulsification. Methods: A randomised, multicentre, parallel-group, triple-masked (participant, outcome assessor, and statistician) trial with 1:1 allocation ratio is proposed. By adopting stratified randomisation (according to cataract grade), we will randomly allocate 480 patients aged >18 years with immature cataract into bevel-up and bevel-down groups at two centres. History of significant ocular trauma, previous intraocular surgery, shallow anterior chamber, low endothelial cell count, pseudoexfoliation syndrome, intraocular inflammation, and corneal endothelial dystrophy are the key exclusion criteria. The primary outcome is postoperative endothelial cell count at one month. Secondary outcomes are central corneal thickness on postoperative days 1, 15, and 30, and intraoperative complications. Trial registration: Clinical Trial Registry of India CTRI/2019/02/017464 (05/02/2019).