Stable Ocular Surface Research Articles

Anti-inflammatory effects of LCB 03-0110 on human corneal epithelial and murine T helper 17 cells.

Dry eye disease (DED) is a complicated disorder that impacts ocular surface and tear-film stability. Inflammation has recently been reported as the core mechanism and main therapeutic target of DED. Although anti-inflammatory drugs have been developed, they still have limited efficacy and various side effects. Recent reports have suggested that kinase inhibitors are beneficial for relieving inflammation. Therefore, this study aimed to investigate the anti-inflammatory effects of LCB 03-0110, a multi-tyrosine kinase inhibitor, on representative cell-based models (HCE- 2 and Th17 cells) of DED. While tacrolimus and tofacitinib, two different anti-inflammatory drugs that have entered clinical trials for DED treatment, did not induce any anti-inflammatory responses in HCE-2 cells, LCB 03-0110 significantly suppressed the phosphorylation of P38 and ERK and reduced the expression levels of IL-6 and IL-8 in HCE-2 cells treated with either LPS or poly(I:C). Moreover, LCB 03-0110 notably decreased the expression level of IL-17A in Th17 cells in a dose-dependent manner, whereas tofacitinib promoted IL-17A production at low concentrations but inhibited its expression at concentrations greater than 1 μM. In addition, LCB 03-0110 was found to be non-toxic to both HCE-2 and Th17 cells. In conclusion, these results suggest that LCB 03-0110 would be a promising drug candidate for the treatment of DED because of its advantages over tacrolimus and tofacitinib.

Use of Plasma Rich in Growth Factors for Ocular Surface Disorders: A Systematic Review.

Ocular surface disorders (OSDs) can severely affect vision and quality of life. Autologous blood products, such as plasma rich in growth factors (PRGF), are recently available to treat OSDs refractory to traditional therapies. This review aims to summarize the efficacy and safety of PRGF in OSDs. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was established a priori and published on PROSPERO (CRD42024522119). MEDLINE, Embase, and Cochrane Library were searched for primary articles until February 6, 2024. Primary outcomes included slit-lamp examination findings and patient-reported outcomes. Secondary outcomes included visual outcomes and adverse events. Risk of bias was assessed using the Cochrane Risk of Bias and ROBINS-I tools. Twenty-two studies involving 1158 eyes were included. PRGF showed notable improvement in objective and subjective outcomes in OSDs. Comparative studies did not show PRGF to be superior to a standard steroid taper for dry eye disease. However, the use of PRGF was also reported in persistent epithelial defects and corneal ulcerations. In these conditions, there were high rates of complete healing and reduced corneal staining. PRGF has also been reported to improve ocular surface healing and stability when used as an adjunct to refractive and pterygium surgeries. No serious adverse events were reported. PRGF has potential as an effective treatment of OSDs resistant to traditional therapies with minimal safety concerns. Large randomized controlled trials are needed to better evaluate the role of PRGF within the treatment armamentarium for corneal pathologies.

Simple limbal epithelial transplantation versus cultivated limbal epithelial transplantation in ocular burns

PurposeTo compare the outcomes of simple limbal epithelial transplantation (SLET) with cultivated limbal epithelial transplantation (CLET) for the management of total limbal stem cell deficiency (LSCD) in eyes with unilateral ocular burns. DesignRandomized controlled trial. Methods100 patients (100 eyes) with unilateral total LSCD following ocular burns undergoing autologous Limbal Stem Cell Transplantation (LSCT) were enrolled and randomized into SLET and CLET groups. Restoration of an epithelized ocular surface was the primary outcome measure. Occurrences of progressive conjunctivalization and persistent epithelial defects postoperatively were considered surgical failures. ResultsMean age was 20.2 ± 13.1 years (SLET) and 22.6 ± 14.3 years (CLET) (p = 0.363). Alkali burn was the most common causative factor in both groups and had comparable mean logMAR BCVA at presentation [SLET: 2.33 ± 0.5, CLET: 2.23 ± 1.48 (p = 0.652)]. Median time interval between injury and surgical intervention was 18 months (SLET) and 12 months (CLET) (p = 0.06). 88 % eyes in SLET group maintained a stable ocular surface at 1 year period versus CLET group (86 %) (p = 0.999). Mean logMAR BCVA significantly improved in both groups with SLET having significantly better BCVA versus CLET at 6 months (p = 0.0390), 1 year (p = 0.0001), 2 year (p = 0.0001) and 3 years (p = 0.0001) follow up. Kaplan-Meier survival analysis was statistically insignificant amongst the 2 groups (p = 0.590). ConclusionsCompared to CLET, SLET is equally efficacious in restoring and maintaining a stable ocular surface in eyes with total LSCD due to ocular burns, with the added advantage of providing superior visual outcomes.

Modified tectonic corneoscleral graft technique for treating devastating corneoscleral infections

BackgroundThis study aims to evaluate the clinical outcomes and efficacy of a modified tectonic corneoscleral graft (TCG) in patients suffering from devastating corneoscleral infections.MethodsThirty-eight eyes from 38 patients who underwent the modified TCG were included in this study. The outcomes measured were recurrence rates, best-corrected visual acuity (BCVA), ocular surface stability, postoperative complications, and graft survival.ResultsAmong the 38 patients, 23 had fungal infections, 9 had bacterial infections and 6 had Pythium insidiosum infections. At the final follow-up, with an average duration of 25.1 ± 8.6 months, the rate of monocular blindness decreased from 100 to 58%. Significant improvements in LogMAR BCVA were observed from preoperative to postoperative measurements (P < 0.001). Thirty-two eyes (84.2%) maintained a stable ocular surface. The survival rate of ocular surface stability was 84.2%±5.9% at one year and 57.7%±9.7% at three years post-surgery. Twenty eyes (52.6%) retained a clear graft, with a survival rate for graft clarity was 81.6%±6.3% at one year and 36.0%±10.8% at three years post-surgery. The incidence of immune rejection was 36.8%. Corneal epithelial defects were observed in ten patients, and choroidal detachment occurred in four patients. No cases of elevated intraocular pressure were detected.ConclusionsThe modified TCG is effective in eradicating infections, preserving the eyeball, and maintaining useful vision in cases of devastating corneoscleral infections. Regular use of tacrolimus, timely administration of glucocorticoids, and good patient compliance can help mitigate postoperative challenges.

Exploring tear viscosity with quartz crystal microbalance technology.

Tear viscosity is a critical property affecting tear distribution and ocular surface stability. While not widely established as a primary diagnostic marker, deviations from normal viscosity can impact ocular health, potentially contributing to conditions such as dry eye syndrome. Despite their importance, traditional viscometers require sample volumes that are not feasible to use with tear volume. This research introduces a novel Quartz Crystal Microbalance (QCM)-based method for tear viscosity measurement, offering a viscometer prototype that operates with minimal sample volumes. Human tear samples, solutions used in artificial eye drops, and various commercial eye drop brands were evaluated. Results show that the QCM method aligns with established viscosity ranges. The average viscosity of healthy human tears was found to be 1.73 ± 0.61 cP, aligning with the typical range of 1-10 cP. Variability in the viscositiesof eye drop can be attributed to differences in their chemical compositions. The QCM method offers benefits such as reduced sample consumption and rapid results, enhancing understanding of tear dynamics for ocular health. Further research with larger sample sizes is needed to establish normative viscosity values in healthy individuals and those with dry eye syndrome, which is crucial for validating the device's clinical efficacy.

A Successfully Treated Case of Invasive Ocular Surface Squamous Neoplasia Involving the Subtotal Cornea in a Monocular Patient: Management in a Resource-Constrained Setting

Abstract: We present a case of a 65-year-old monocular patient who was clinically diagnosed with ocular surface squamous neoplasia covering all but 2 clock hours of the limbus and almost the entire cornea. He underwent complete tumor excision followed by amniotic membrane transplantation. Postexcision, the patient had a clear cornea and stable ocular surface without inflammation or recurrence for 18 months of follow-up. The visual acuity improved to 6/18 from count fingers at face. The histopathology result uncovered squamous cell carcinoma of conjunctiva and cornea. The absence of recurrence can be attributed to complete excision and intraoperative mitomycin C.

Reducing tension step by step in epicanthus and lower eyelid incision for treating cilial entropion in children: A case series analysis

ObjectiveTo evaluate the surgical outcomes of a modified technique for treating congenital cilial entropion in children, which involves reducing tension step by step in the epicanthus and lower eyelid incision. MethodsThe observational group consisted of 153 pediatric patients (81 males and 72 females) who were treated using the modified technique, whereas the control group included 124 patients (68 males and 56 females) who were treated using the rotating suture surgery. All the participants were bilateral. Surgical outcomes were classified as good, fair, or poor, and the recurrence rate, scar condition, inferior eyelid position, and patient satisfaction were also assessed. ResultsThe mean follow-up period was 9.13 ± 3.50 months (range: 3–14 months) for the observational group and 6.93 ± 4.51 months (range: 3–14 months) for the control group. In the observational group, surgical success with "good" outcomes was achieved in 300 eyes (98.04%), compared to 224 eyes (90.32%) in the control group. No recurrence occurred in the observational group, whereas the recurrence rate in the control group was 4.43%. Postoperative scar formation was mild in the observational group. The average scar score was 1.27 ± 0.96 in the observational group and 2.70 ± 0.99 in the control group, with a statistically significant difference (P < 0.001). Neither overcorrection nor postoperative ectropion was observed in both groups. ConclusionThe modified technique effectively corrected medial entropion and trichiasis in the lower eyelid, resulting in stable postoperative outcomes, mild scar formation, quick recovery, flexible eyelid motility, and stable ocular surface. Therefore, it can be widely applied to children with congenital entropion and trichiasis.

Dry Eye Disease Symptoms Among Glaucoma Patients at a Portuguese Hospital.

Glaucoma-related dry eye disease (DED) is often underestimated, but it is an important comorbidity affecting 40% to 59% of glaucoma patients. It may be an exacerbation of a pre-existing condition or a novel disease starting after the initiation of topical medication. The cumulative effect of medication, preservatives and excipients leads to an alteration in tear film composition and ocular surface stability. The main purpose of this investigation was to study a group of Portuguese glaucoma patients regarding the presence of DED symptoms and correlate the severity of the symptoms with the usage of different types of glaucoma topical medications. This is a cross-sectional observational study of patients diagnosed with primary and secondary open-angle glaucoma. The questionnaire Standardized Patient Evaluation of Eye Dryness (SPEED) translated to Portuguese (SPEED-Vp) was taken by patients followed in the Glaucoma Department of Unidade Local de Saúde Entre Douro e Vouga, Santa Maria da Feira, Portugal. Data was collected regarding their age, gender, type of topical medication in use as well as frequency and duration of usage. A statistical analysis was performed. A total of 75 patients answered the SPEED-Vp questionnaire. The mean age was 72 ± 7 years old. Fifty-two percent (n=39) were male, and 48% (n=36) were female patients. About 49.33% (n=37) had been on intraocular pressure (IOP)-lowering eyedrops for more than five years. About 61.43% (n=43) of patients used IOP-lowering eyedrops with preservatives. Most of the patients used prostaglandin analogs (75.71%, n=53) and beta-blockers (72.86%, n=51). SPEED score average was 2.75. About 25.33% (n=19) had no DED symptoms, 58.67% (n=44) had mild symptoms, 8% (n=6) had moderate symptoms and 8% (n=6) had severe symptoms. No statistically significant correlation was found between SPEED score and age, gender, number of eyedrop containers, number of active principles, application frequency, presence of preservatives, number of eyedrop containers with preservatives, duration of eyedrops usage or any of the medication groups. Although a high percentage of patients were on eyedrops with preservatives, this low rate of symptoms might be because patients tended to devalue these symptoms;were already on treatment with artificial tears; or have an underestimation of the sensation of dry eye due to decreased neuronal corneal nerve responses and density. These results were surprisingly positive. This might also be the result of the healthcare provider's sensibilization to this issue (early diagnosis, early prescription of artificial tears and change from preservative to preservative-free medication).

Allogenic Simple Limbal Epithelial Transplantation: An Approach to Bilateral Recurrent Pterygia and Limbal Stem Cell Deficiency

Abstract: A 44-year-old man presented with bilateral total limbal stem cell deficiency after multiple failed surgeries for recurrent pterygia in both eyes over the last 11 years. His best corrected visual acuity (BCVA) in both eyes at the time of presentation was hand movement, projection of rays accurate. Owing to bilateral involvement, allogenic simple limbal epithelial transplantation (Allo SLET) was performed in the right eye. The limbal biopsy was taken from the wife of the patient. Complete ocular surface epithelialization was achieved in 26 days. The patient has completed 15 months of postoperative follow-up with stable ocular surface and BCVA 6/12 in the RE. He is on systemic and topical immunosuppressants with no side effects to date.

Long-term ocular surface stability in conjunctivolimbal autograft and ocular surface safety in the donor eyes.

The current study is aimed to present the long-term results of the patients who underwent conjunctivolimbal autograft (CLAU) as the primary operation in unilateral limbal stem cell deficiency and the ocular surface safety of the donor eyes. The patients were followed up for fiveyears or longer. The records of all patients who underwent CLAU as the primary operation were retrospectively analyzed. Additional ocular surface operations, ocular surface stability, best-corrected visual acuity (BCVA), and ocular surface status of the donor eyes were investigated. The mean age of the patients at the time of transplantation was 35.07 ± 12.9 (12-60). Twenty-nine eyes of 29 patients were followed up for an average of 97.82 ± 34.45 (60-186) months. Additional ocular surface operation was required in 27.58% (8/29) of the eyes in order to achieve a stable ocular surface. Ocular surface stability was achieved in 82.75% (24/29) of the eyes at the end of the follow-up period. BCVA increased from 1.78 ± 0.82 to 0.91 ± 0.92 logMAR at the last visit (p < 0.001). Corneal ectasia and vascularization developed in one donor eye in the fifth postoperative year. CLAU tissues provide ocular surface stability with a successful vision result in the long term. CLAU theoretically carries risks including limbal stem cell deficiency in the donor eye. In the long-term follow-up of donor eyes after CLAU, ectasia and limbal stem cell deficiency were observed in one eye.

Conjunctival flap surgery for traumatic corneal ulcers

Introduction : Trauma was the most common risk factor for corneal ulcers and blindness. Death of corneal tissue due to loss of part of the surface of the cornea is called a corneal ulcer. Conjunctival flap (CF) surgery has an acknowledged role in assuring a stable ocular surface and repressing inflammation in compromised corneas or eyes with reduced visual potential.&#x0D; Case Illustration : 26-year- old male patient came to the Chasan Boesorie Ternate Hospital polyclinic with pain in the left eye after splash cement 3 days before being admitted to the hospital. The left eye is runny, feels itchy, looks red and like there is a block and glare. On ophthalmology status there was a visual acuity OD 6/6, OS 1/300, OS cloudy cornea, hypopion, prolapse of iris and central corneal ulcer with a size of ± 2 x 1 mm.&#x0D; Discussion : The remaining flaps were performed for corneal perforation, graft rejection, bullous keratopathy, and secondary corneal edema. Conjunctival flaps have previously proven to be effective in preserving the globe for individuals with severe ocular surface disease. The flaps promote nutrition, metabolism, structure, and vascularity, as well as reduce pain, irritation, inflammation, and infection. After 6 weeks of surgery visual acuity become better, OS 20/200.&#x0D; Conclusion : Conjunctival flap surgery is an important and useful surgical option of ocular surface disease, especially recalcitrant infectious keratitis and corneal ulcers, particularly in nonresponsive and some perforated cases. CF procedure went well, provides mechanical support for corneal wound healing with good visual outcomes on the patient.

Comparative analysis of long-term results of three epithelial cell transplantation procedures for treating limbal stem cell deficiency

This study compared the long-term outcome of different epithelial transplantation techniques to treat limbal stem cell deficiency (LSCD). We conducted a retrospective 15-year comparative systematic cohort study of patients with LSCD who underwent either cultivated limbal epithelial transplantation (CLET), simple limbal epithelial transplantation (SLET), or cultivated oral mucosal epithelial transplantation (COMET). We reviewed the demographic data, etiology, LSCD severity, best-corrected visual acuity, surgical outcomes, and complications. A total of 103 eyes of 94 patients (mean age, 45.0 ± 16.4 years) with LSCD were enrolled. The most common cause of LSCD was chemical injury (42.7 %). The median follow-up time was 75 months. The success rates of CLET, SLET, and COMET were 45.5 %, 77.8 %, and 57.8 %, respectively. The 7-year survival rates after CLET, SLET, and COMET were 50.0 %, 72.2 %, and 53.2 %, respectively. Steven-Johnson syndrome (SJS) had a significantly lower survival rate than other causes (p < 0.001), but SLET had a significantly higher survival rate than CLET (p = 0.018) and COMET (p = 0.047). Visual improvement of more than four Snellen lines was achieved in 53.1 % of successful cases and 28.2 % of failed cases. SJS, Schirmer I test <5 mm, and the presence of postoperative recurrent epithelial defects were significant risk factors for a failed surgery. All epithelial transplantation techniques had favorable long-term surgical outcomes. More than half of the patients achieved a stable ocular surface and visual acuity improvement up to 7 years postoperatively. SLET tends to have a better surgical outcome than CLET and COMET, especially in patients with SJS.

Long‐term clinical course of amniotic membrane after permanent amniotic membrane transplantation

Aims/Purpose: To investigate the long‐term clinical outcomes of transplanted amniotic membrane in patients who underwent permanent amniotic membrane transplantation (P‐AMT) on cornea.Methods: From April 2014 to March 2021, medical records and digital photographs of 68 patients (72 eyes) who underwent P‐AMT were analysed retrospectively. The duration of complete re‐epithelization of cornea and wearing therapeutic contact lens (T‐lens) after surgery were investigated, the size of preserved amniotic membrane (AM) excluding the melted portion was analysed using the Image J program every year up to 6 years after surgery, and it was compared by dividing into a single‐layer group and a double‐layer group. In addition, when the AM melts, the cause, time, and related factors of melting were analysed.Results: The average duration to complete re‐epithelialization after surgery was 12.2 ± 11.0 days, and T‐lens were worn on average up to 8.7 ± 8.5 months after surgery. In total group, the average ratio of preserved AM annually up to 6 years after surgery was 94.9%, 94.3%, 97.8%, 96.4%, 95.8%, 91.6% respectively, and there was no significant difference between the single‐layer group and the double‐layer group. AM melting appeared in 38.9% (28 eyes) of the total group, and melting was first observed on average 16.4 ± 17.2 months after surgery. The formation and rupture of bullae was the most common cause of melting at 71.4% (20 eyes), and there were no statistically significant related factors involved in the formation of bullae.Conclusions: In the case of P‐AMT performed in various diseases of the cornea, the transplanted AM is partially melt but considered to be well preserved up to 6 years after surgery to form a stable ocular surface.

Case Report: Simultaneous penetrating keratoplasty with autologous simple limbal epithelial transplantation as an alternative to keratoprosthesis

Introduction and importance: This case report highlights the multidisciplinary approach required to achieve successful anatomical and functional outcomes, in an eye with total limbal stem cell deficiency (LSCD) associated with underlying corneal scarring and thinning. Presentation of case: A 59-year-old gentleman had poor visual recovery in the right eye (RE) following accidental carbide blast, 1-year before presenting to us. The visual acuity was counting fingers and clinical examination revealed cicatricial entropion involving the upper eyelid, total LSCD, corneal scarring with a central descemetocele and cataract in the RE. Prior to ocular surface reconstruction, entropion correction was performed. Three months later, penetrating keratoplasty combined with cataract surgery and intraocular lens implantation (penetrating keratoplasty (PK) triple), with autologous simple limbal epithelial transplantation (SLET) was performed. The visual acuity was 20/100, 18 months after the surgery, with a clear well-epithelized corneal graft and stable ocular surface. Discussion: LSCD is caused by a decrease in the population and /or function of the limbal epithelial stem cells. Limbal stem cell transplantation (LSCT) is warranted in eyes with total LSCD. In eyes with coexisting corneal scarring, LSCT alone may be inadequate to restore the vision. These eyes require simultaneous or sequential lamellar or full-thickness corneal transplantation for visual rehabilitation. Though, the existing literature favors a sequential approach, where LSCT is performed first followed by corneal transplantation, under certain circumstances such as a thin underlying cornea like in our case, corneal transplantation may have to be combined with LSCT to achieve optimal outcomes. Conclusion: Combining autologous SLET with PK can be performed for visual rehabilitation in eyes with unilateral total LSCD and underlying corneal thinning. Corneal and limbal graft survival is prolonged if existing adnexal comorbidities are addressed before any surgical intervention is planned and adequate time interval is allowed for the surface inflammation to subside.

Case Report: Simultaneous penetrating keratoplasty with autologous simple limbal epithelial transplantation as an alternative to keratoprosthesis

Introduction and importance: This case report highlights the multidisciplinary approach required to achieve successful anatomical and functional outcomes, in an eye with total limbal stem cell deficiency (LSCD) associated with underlying corneal scarring and thinning. Presentation of case: A 59-year-old gentleman had poor visual recovery in the right eye (RE) following accidental carbide blast, 1-year before presenting to us. The visual acuity was counting fingers and clinical examination revealed cicatricial entropion involving the upper eyelid, total LSCD, corneal scarring with a central descemetocele and cataract in the RE. Prior to ocular surface reconstruction, entropion correction was performed. Three months later, penetrating keratoplasty combined with cataract surgery and intraocular lens implantation (penetrating keratoplasty (PK) triple), with autologous simple limbal epithelial transplantation (SLET) was performed. The visual acuity was 20/100, 18 months after the surgery, with a clear well-epithelized corneal graft and stable ocular surface. Discussion: LSCD is caused by a decrease in the population and /or function of the limbal epithelial stem cells. Limbal stem cell transplantation (LSCT) is warranted in eyes with total LSCD. In eyes with coexisting corneal scarring, LSCT alone may be inadequate to restore the vision. These eyes require simultaneous or sequential lamellar or full-thickness corneal transplantation for visual rehabilitation. Though, the existing literature favors a sequential approach, where LSCT is performed first followed by corneal transplantation, under certain circumstances such as a thin underlying cornea like in our case, corneal transplantation may have to be combined with LSCT to achieve optimal outcomes. Conclusion: Combining autologous SLET with PK can be performed for visual rehabilitation in eyes with unilateral total LSCD and underlying corneal thinning. Corneal and limbal graft survival is prolonged if existing adnexal comorbidities are addressed before any surgical intervention is planned and adequate time interval is allowed for the surface inflammation to subside.

Development of a novel protocol to evaluate contact-lens related ocular surface health on marmosets (Callithrix jacchus)

Contact lens wear affects the ocular surface and can cause contact lens-induced dry eye (CLIDE). The purpose of this study was bifold: (1) to develop a novel protocol to assess the ocular surface in a non-human primate (NHP) model, the common marmoset (Callithrix jacchus), and (2) to characterize central corneal thickness (CCT), tear osmolarity, blink rate and tear meniscus height (TMH) longitudinally, in untreated marmosets (controls) compared to animals treated with contact lenses (CL). Longitudinal changes in CCT (N = 10 control; N = 10 treated with contact lenses, CL-treated), osmolarity (N = 4 control; N = 6 CL-treated), blink rate (N = 8 control; N = 10 CL-treated) and TMH (N = 8 control; N = 6 CL-treated) were assessed using high frequency A-scan ultrasound, the I-PEN Vet Tear Osmolarity System, a video recording system (745 frames/minute) and Image J respectively, from 70 days to 224 days (5 months) at approx. 9am, and again after 9hrs of CL wear (methafilcon A, 55% water content; Capricornia, Australia) after every 4 weeks of contact lens wear for a total of 22 weeks of treatment. Repeated measures ANOVA was used to compare eyes over time and student t-test was used to compare treated to control eyes at each time point. At baseline, untreated marmosets had a CCT (mean ± SD) of 0.31 ± 0.01 mm, tear osmolarity 311.67 ± 11.48 mOsms/L, blink rate 1.83 ± 1.79 blinks per minute (bpm) and TMH 0.07 ± 0.02 arbitrary units (au), all of which remained stable over 5 months, except blink rate that increased to 5.32 ± 1.58 bpm (p < 0.01) after 5 months. In CL-treated marmosets, however, CCT progressively increased with CL wear (baseline: 0.30 ± 0.01 mm; 5 months: 0.31 ± 0.02 mm, p < 0.05), while osmolarity decreased after 2 and 3 months of CL wear (baseline: 316.11 ± 13.63; 2 months: 302.63 ± 11.27, p < 0.05; 3 months: 302.92 ± 14.58, p < 0.05). The decrease in osmolarity occurred in parallel to an increase in blink rate (baseline: 0.98 ± 1.18 bpm; 2 months: 3.46 ± 3.04 bpm, p < 0.05; 3 months: 3.73 ± 1.50 bpm, p < 0.001). TMH decreased during the third month of CL wear (baseline: 0.06 ± 0.00 au; 3 months: 0.05 ± 0.01 au, p < 0.05), and increased after 4 months (0.08 ± 0.01 au, p < 0.05). As TMH decreased, tear osmolarity increased in both control (R = −0.66, p < 0.05) and CL-treated marmosets (R = −0.64, p < 0.05). The results suggest that marmosets treated with CL for 5 months experienced an increase in blink rate, CCT and TMH, along with a decrease in osmolarity within the first few months of CL treatment that differed from the unaffected stable ocular surface findings observed untreated animals. We hypothesize that CL wear in marmosets might induce an increased blink rate and TMH, in turn delaying the development of hyperosmolarity. These findings confirm that the marmoset is a good novel animal model for ocular surface research for the assessment of novel contact lens materials aimed to alleviate CLIDE.

Long-Term Benefits of Tear Exchangeable Limbal-Rigid Contact Lens Wear Therapy in Stevens-Johnson Syndrome Cases.

To evaluate the long-term benefits of tear-exchangeable, limbal-rigid contact lens (CL) wear therapy in patients with Stevens-Johnson syndrome (SJS)-associated ocular sequelae. This retrospective study evaluated 50 eyes of 41 SJS patients (15 men and 26 women) who underwent limbal-rigid CL wear therapy for more than 2 years post fitting. Ocular sequelae (i.e., conjunctival hyperemia, corneal neovascularization, and upper tarsus scarring) before fitting and at 3 months, 6 months, 12 months, and annually after initiating CL wear therapy were evaluated and then graded on a severity score (range: 0-3, maximum score: 3). Moreover, visual acuity (VA) at immediately post initiating CL wear therapy was evaluated. The mean follow-up period was 4.3±1.1 years. Compared with before fitting, the mean conjunctival hyperemia score improved from 1.14 to 0.86 at 3 months of CL wear therapy ( P <0.01) and was maintained thereafter; the mean corneal neovascularization score improved from 2.10 to 1.98 at 3 months of CL wear therapy, with no deterioration of the score observed in all cases at the final follow-up examination, and mean VA (log of minimum angle of resolution) improved from 1.60 to 1.04 at immediately post initiating CL wear therapy ( P <0.01). Limbal-rigid CL wear therapy can provide long-term ocular surface stabilization and improved VA in SJS patients.

Successful restoration of corneal surface integrity with a tissue-engineered allogeneic implant in severe keratitis patients

ObjectivesCorneal diseases are among the main causes of blindness, with approximately 4.6 and 23 million patients worldwide suffering from bilateral and unilateral corneal blindness, respectively. The standard treatment for severe corneal diseases is corneal transplantation. However, relevant disadvantages, particularly in high-risk conditions, have focused the attention on the search for alternatives. MethodsWe report interim findings of a phase I-II clinical study evaluating the safety and preliminary efficacy of a tissue-engineered corneal substitute composed of a nanostructured fibrin-agarose biocompatible scaffold combined with allogeneic corneal epithelial and stromal cells (NANOULCOR). 5 subjects (5 eyes) suffering from trophic corneal ulcers refractory to conventional treatments, who combined stromal degradation or fibrosis and limbal stem cell deficiency, were included and treated with this allogeneic anterior corneal substitute. ResultsThe implant completely covered the corneal surface, and ocular surface inflammation decreased following surgery. Only four adverse reactions were registered, and none of them were severe. No detachment, ulcer relapse nor surgical re-interventions were registered after 2 years of follow-up. No signs of graft rejection, local infection or corneal neovascularization were observed either. Efficacy was measured as a significant postoperative improvement in terms of the eye complication grading scales. Anterior segment optical coherence tomography images revealed a more homogeneous and stable ocular surface, with complete scaffold degradation occurring within 3–12 weeks after surgery. ConclusionsOur findings suggest that the surgical application of this allogeneic anterior human corneal substitute is feasible and safe, showing partial efficacy in the restoration of the corneal surface.

WNT16b promotes the proliferation and self-renewal of human limbal epithelial stem/progenitor cells via activating the calcium/calcineurin A/NFATC2 pathway.

Our previous finding revealed that WNT16b promoted the proliferation of human limbal epithelial stem cells (hLESCs) through a β-catenin independent pathway. Here, we aimed to explore its underlying molecular mechanism and evaluate its potential in the treatment of limbal stem cell deficiency (LSCD). Based on the findings of mRNA-sequencing, the expression of key molecules in WNT/calcineurin A/NFATC2 signalling pathway was investigated in WNT16b-co-incubated hLESCs and control hLESCs. An epithelial wound healing model was established on Wnt16b-KO mice to confirm the regulatory effect of WNT16b in vivo. The therapeutic potential of WNT16b-co-incubated hLESCs was also evaluated in mice with LSCD. Our findings showed that WNT16b bound with Frizzled7, promoted the release of Ca2+ and activated calcineurin A and NFATC2. With the translocation of NFATC2 into cell nucleus and the activation of HDAC3, WDR5 and GCN5L2, the expression of H3K4me3, H3K14ac and H3K27ac in the promoter regions of FoxM1 and c-MYC increased, which led to hLESC proliferation. The effect of the WNT16b/calcium/calcineurin A/NFATC2 pathway on LESC homeostasis maintenance and corneal epithelial repair was confirmed in Wnt16b-KO mice. Moreover, WNT16b-coincubated hLESCs could reconstruct a stable ocular surface and inhibit corneal neovascularization in mice with LSCD. In conclusion, WNT16b enhances the proliferation and maintains the stemness of hLESCs by activating the non-canonical calcium/calcineurin A/NFATC2 pathway in vitro and in vivo, and accelerates corneal epithelial wound healing.

Long-term Clinical Course of Amniotic Membrane after Permanent Amniotic Membrane Transplantation

Purpose: To investigate the long-term clinical outcomes of transplanted amniotic membrane in patients who underwent permanent amniotic membrane transplantation (P-AMT) on cornea.Methods: From April 2014 to March 2021, medical records and digital photographs of 68 patients (72 eyes) who underwent P-AMT were analyzed retrospectively. The duration of complete re-epithelization of cornea and wearing therapeutic contact lense (T-lens) after surgery were investigated, the size of preserved amniotic membrane (AM) excluding the melted portion was analyzed using the Image J program every year up to 6 years after surgery, and it was compared by dividing into a single-layer group and a double-layer group. In addition, when the AM melts, the cause, time, and related factors of melting were analyzed.Results: The average duration to complete re-epithelialization after surgery was 12.2 ± 11.0 days, and T-lens were worn on average up to 8.7 ± 8.5 months after surgery. In total group, the average ratio of preserved AM annually up to 6 years after surgery was 94.9%, 94.3%, 97.8%, 96.4%, 95.8%, 91.6% respectively, and there was no significant difference between the single-layer group and the double-layer group. AM melting appeared in 38.9% (28 eyes) of the total group, and melting was first observed on average 16.4 ± 17.2 months after surgery. The formation and rupture of bullae was the most common cause of melting at 71.4% (20 eyes), and there were no statistically significant related factors involved in the formation of bullae.Conclusions: In the case of P-AMT performed in various diseases of the cornea, the transplanted AM is partially melt but considered to be well preserved up to 6 years after surgery to form a stable ocular surface.