Neurotrophic keratopathy: General features and new therapies.

Neurotrophic keratopathy is an uncommon degenerative corneal disorder characterized by compromised corneal sensory innervation, resulting in the formation of epithelial defects and nonhealing corneal ulcers. Various treatment modalities are available to stabilize disease progression, improve patient well-being, and prevent vision loss. For eligible patients, medical and surgical reinnervation have emerged as pioneering therapies, holding promise for better management. This article presents a comprehensive review of the disease, providing an update relevant to ophthalmologists on pathogenesis, diagnosis, treatment options, and novel therapies targeting pathophysiological pathways.

Importance and use of corneal biomechanics and its diagnostic utility.

The study of corneal biomechanics has become relevant in recent years due to its possible applications in the diagnosis, management, and treatment of various diseases such as glaucoma, keratorefractive surgery and different corneal diseases. The clinical biomechanical investigation has become of great importance in the setting of refractive surgery to identify patients at higher risk of developing iatrogenic ectasia. This review focuses on two of the technologies available for clinical use, the Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, NY, USA) and the Corvis ST (Oculus Optikgergäte GmbH, Wetzlar, Germany). Both are non-contact tonometers that provided a clinical evaluation of corneal biomechanics. The fundamentals and main parameters of each device are described, as well as their use in eye surgery and the corneal biomechanical behavior in eye diseases. Finally, we will discuss the more recent Brillouin microscopy biomechanical analysis, and the integration Scheimpflug-based corneal tomography and biomechanical data with artificial intelligence to increase accuracy to detect risk of ectasia.

El estudio de la biomecánica corneal ha cobrado relevancia en los últimos años debido a sus posibles aplicaciones en el diagnóstico, el manejo y el tratamiento de diversas enfermedades, como glaucoma, cirugía queratorrefractiva y diferentes enfermedades corneales. La investigación de la biomecánica corneal es de mucha importancia en el contexto de cirugía refractiva, pues podría identificar pacientes en riesgo de desarrollar una ectasia corneal iatrogénica. Esta revisión se centra en dos de las tecnologías disponibles para uso clínico: el Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, NY, EE. UU.) y el Corvis ST (Oculus Optikgergäte GmbH, Wetzlar, Alemania). Ambos son tonómetros de no contacto que proporcionan una evaluación clínica de la biomecánica corneal. Se describen los fundamentos y los principales parámetros de cada dispositivo, así como su uso en cirugía ocular y el comportamiento biomecánico corneal en las enfermedades oculares. Finalmente, se mencionan los dispositivos más recientes de análisis biomecánico, como la microscopía de Brillouin, así como la integración de los datos biomecánicos y topográficos basados en Scheimpflug con la inteligencia artificial para aumentar la precisión en la detección del riesgo de ectasias.

Cogan syndrome: a case report and review of the literature.

Cogan syndrome is a rare disease whose etiology is still undetermined. It typically affects men and women between the second and fourth decade of life. We report a case of Cogan syndrome with ocular and audio-vestibular involvement as a systemic manifestation in a 31-year-old woman.

Use of Amniotic Membrane Transplant and Deep Anterior Keratoplasty in a Patient with Bilateral Acanthamoeba Infectious Keratitis: A Case Report.

The aim of this study was to report a case with the use of amniotic membrane transplant and deep anterior keratoplasty in a patient with bilateral Acanthamoeba infectious keratitis as a treatment. A 20-year-old male presented with bilateral Acanthamoeba keratitis (AK) who was initially diagnosed with herpetic keratitis receiving full antiviral and corticosteroid topical treatment without any improvement. Corneal biopsy was performed to confirm the suspected diagnosis, and Acanthamoeba stromal cysts were identified in the sample. Treatment was initiated with 0.02% chlorhexidine, 0.1% propamidine isethionate, neomycin, and tropicamide/phenylephrine. Symptoms and clinical improvement were achieved between the 8th and 10th weeks, so corticosteroids were initiated. Treatment was continued until we observed a poor response in the left eye; therefore, an epithelial scraping and amniotic membrane placement were performed. Lately, the right eye underwent a deep anterior lamellar keratoplasty. A challenging case of bilateral AK managed with topical medications, amniotic membrane, and corneal keratoplasty. The earlier the disease is diagnosed, the better the outcome. If the diagnosis is delayed, the amoebas have penetrated deep into the corneal stroma, and successful therapy becomes difficult. A surgical option can be an early solution with a good prognosis for these cases.

Comparison of mini-simple limbal epithelial transplantation and conjunctival-limbal autograft for the treatment of primary pterygium: a randomised controlled trial.

PURPOSE: The purpose of this double-masked, parallel randomised controlled trial was to compare the recurrence rate and other outcomes between conjunctival-limbal autograft (CLAu) and mini-simple limbal epithelial transplantation (mini-SLET) after excision of pterygium. METHODS: Eligibility criteria for participants was the presence of a primary nasal pterygium extending equally to or greater than two millimetres on the cornea on its horizontal axis from the nasal limbus. The participants were allocated into two groups (CLAu and mini-SLET) using simple randomisation with a table of random numbers. Participants and the outcome assessor were masked to the intervention. The study protocol is listed and available on https://clinicaltrials.gov (Identifier: NCT03363282). RESULTS: A total of 61 eyes were enrolled in the study, 33 underwent CLAu (group 1) and 28 mini-SLET (group 2), all eyes were analysed in each group. At 2, 3, 6 and 12 months the CLAu group exhibited a recurrence of 0%, 6.1%, 8.1% and 8.1%, while the mini-SLET exhibited a recurrence of 0%, 17.9%, 50% and 53.5% (p<0.05). There were no intraoperative or postoperative complications in either of the two groups. CONCLUSION: The findings of this study suggest that mini-SLET has a higher recurrence rate and provides no advantage over CLAu in the treatment of primary pterygium.

Adjuvant Topical Interferon Alpha 2b for the Treatment of Monkeypox Ocular Manifestations.

PURPOSE: The aim of this study was to report a case of ocular Mpox that responded favorably to treatment with topical interferon and oral doxycycline. METHODS: This is a case report of a previously healthy 24-year-old woman who developed a pustular rash, headache, fever, arthralgia, sore throat, and asthenia 3 weeks before attending to our clinic. Her main complaint at the moment of the visit was pain, photophobia, foreign body sensation, blurred vision, red eye, and discharge on the left eye. The slit-lamp examination of the left eye showed severe conjunctival hyperemia associated with tarsal follicles, 360 degrees ciliary injection, diffuse corneal epithelial edema with white linear epithelial infiltrates, pigmented and nonpigmented keratic precipitates, and two 1-mm peripheral corneal ulcers with white infiltrates, associated with positive fluorescein staining. Anterior chamber cellularity and flare were mildly present. RESULTS: Mpox with ocular manifestations diagnosis was confirmed by real-time quantitative reverse transcription polymerase chain reaction assay (qRT-PCR) testing; samples were taken from corneal, conjunctival, and nasopharynx swab as well as a skin scab. Topical interferon alpha 2b 1 MIU/mL every 6 hours for 1 month and oral doxycycline 100 mg BID were administered along with other medications with consequent decrease of inflammation and malaise symptoms 1 week later, associated with uncorrected visual acuity improvement. CONCLUSIONS: Alternative and efficacious treatment options for Mpox ocular manifestations are needed to prevent further disease progression and sequelae in countries with no access to the gold-standard therapy. Topical interferon alpha 2b and oral doxycycline have shown adequate response as shown with this patient.

Concomitant Bandage Contact Lens, Oral Nicergoline, and Topical Autologous Serum for Severe Neurotrophic Keratitis.

BACKGROUND: To report the outcomes of using the combination of oral nicergoline, autologous serum, and contact lens to enhance corneal epithelization in neurotrophic keratitis and to discuss the clinical potential of this management. METHODS: This was a prospective consecutive case series study of eight patients treated for neurotrophic keratitis at the "Conde de Valenciana" Institute of Ophthalmology. Oral nicergoline, autologous serum, and bandage contact lens were initiated at the same time, immediately after stage 3 diagnosis keratitis was confirmed clinically, and until corneal epithelialization was achieved or eminent corneal perforation was seen. In patients where diabetes was a cause, glycosylate hemoglobin was measured to asses metabolic control. Corneal esthesiometry and corrected distance visual acuity were assessed before and after treatment. RESULTS: This study included eight eyes of eight patients (5 men [62.5%], average age 57±17.9 years). All patients completed at least 1 month of follow-up after nicergoline and contact lens suspension. Of the eight eyes, no one had positive culture growth and complete epithelial healing was achieved in all cases. Half of patients had diabetes and had a poor metabolic control. Corneal sensitivity improved in all eyes almost 2 centimeters in Cochet-Bonnet esthesiometry ( P= 0.01). In addition, final visual acuity gains were obtained ( P= 0.100). CONCLUSIONS: The combination of oral nicergoline, autologous serum, and bandage contact lens simultaneously could be an alternative in the management of stage 3 neurotrophic keratitis when conventional medical treatment has no improvement of corneal epithelization.

Delayed-onset pressure-induced interlamellar stromal keratitis (PISK) and interface epithelial ingrowth 10 years after laser-assisted in situ keratomileusis.

Purpose: To report a case of pressure-induced interlamellar stromal keratitis (PISK) 10 years after laser assisted in situ keratomileusis (LASIK). Observations: A case of a 36-year-old man who underwent LASIK and presented with PISK 10 years later. Before presenting to our department he consulted elsewhere for red eye, decreased visual acuity, foreign body sensation, and pain on the RE for 1 week. He was then prescribed topical prednisolone six times per day and was lost to follow-up. On examination and after 1 month of continuous use of steroids uncorrected distance visual acuity (UCDV) was 20/400 in the right eye (RE) and 20/20 in the left eye (LE). Best corrected visual acuity was 20/80 on the RE. The Goldmann intraocular pressure (IOP) was 26 and 17 mmHg in the RE and LE, respectively. Slit lamp biomicroscopy revealed fluid in the interface and epithelial ingrowth. Fundoscopic examination results were normal in both eyes. Treatment was initiated with topical brimonidine tartrate 0.2%, timolol 0.5%, and dorzolamide 2.0% BID. Once the pressure was controlled the patient was scheduled for mechanical debridement of the epithelial ingrowth with significant improvement of UCVA (20/25). Conclusions: Refractive surgeons should be aware of PISK as a potential complication of LASIK even years after the procedure. Intraocular pressure can be misleading, and diligent and careful examination are key to diagnosis and treatment of this potentially blinding complication.

Safety and efficacy of pilocarpine, cevimeline, and diquafosol compared to artificial tears for the treatment of dry eye: protocol for a systematic review.

BACKGROUND: Dry eye disease (DED) is a condition that compromises the ocular surface and affects millions of people around the world. In recent years, a scheme has been proposed for the treatment of DED, with the use of artificial tear being the mainstay of treatment. In this scheme, the use of secretagogues is suggested as part of the treatment for patients with moderate to severe affectation. With this systematic review, we aim to evaluate the effectiveness and safety of secretagogues for DED. METHODS: Electronic databases will be searched; we will include randomized controlled trials that compare secretagogues and artificial tears. Study inclusion will not be restricted on the basis of language or publication status. We will use Google Translate to assess studies written in languages other than English and Spanish. Identification, evaluation, data extraction, and assessment of risk of bias will be conducted by two authors of the review, a third review author will resolve any disagreement. The outcomes will be the ocular surface disease index score, tear film break-up time, Schirmer test score, VRQoL Score, and tear film osmolarity. We will use the Cochrane Collaboration Risk of Bias 2 (RoB 2) tool for assessing the risk of bias of the included studies. Based on the heterogeneity of the included studies, we will combine the findings in a meta-analysis using a fixed effect model if heterogeneity ≤ 50% or a random effect model if heterogeneity > 50%. If we deem meta-analysis as inappropriate, we will document the reasons and report findings from the individual studies narratively. DISCUSSION: Based on the evidence obtained, we will evaluate the effect of pilocarpine, cevimeline, and diquafosol and compare it to artificial tears on multiple outcome measures. This systematic review aims to determine the efficacy and safety of the secretagogues pilocarpine, cevimeline, and diquafosol to help clinicians in the decision-making process. TRIAL REGISTRATION: PROSPERO CRD42020218407 .

A Practical Approach to Severity Classification and Treatment of Dry Eye Disease: A Proposal from the Mexican Dry Eye Disease Expert Panel.

Dry eye disease (DED) has a higher prevalence than many important systemic disorders like cardiovascular disease and diabetes mellitus, representing a significant quality of life burden for the affected patients. It is a common reason for consultation in general eye clinics worldwide. Nowadays, the diagnostic and therapeutic approach at the high corneal and ocular surface specialty level should be reserved for cases of severe and chronic dry eye disease associated with systemic autoimmune diseases or complicated corneal and ocular surface pathologies. In such cases, the diagnostic and therapeutic approach is often complex, elaborate, time-consuming, and costly due to the use of extensive dry eye questionnaires, noninvasive electronic diagnostic equipment, and clinical laboratory and ancillary tests. However, other eye care specialists attend a fair amount of DED cases; therefore, its diagnosis, classification, and management should be simple, practical, achievable, and effective. Considering that many patients attending non-specialized dry eye clinics would benefit from better ophthalmological attention, we decided to elaborate a practical DED classification system based on disease severity to help clinicians discriminate cases needing referral to subspecialty clinics from those they could attend. Additionally, we propose a systematic management approach and general management considerations to improve patients' therapeutic outcomes according to disease severity.

Optical coherence tomography findings of cyanoacrylate glue patch in corneal perforations.

Purpose: To report a cases series of corneal perforations treated with cyanoacrylate glue patch (CGP) assessed with optical coherence tomography for monitoring corneal status in long-term follow-up examinations. Observations: CPG was successfully used as primary treatment in three cases of corneal perforations. Spontaneous loosening or dislodging of the CPG did not occur in the follow-up. Anterior segment optical coherence tomography (AS-OCT) was performed to monitor wound healing at the site of perforation before considering the CGP removal. The presence of normal epithelium layer beneath the glue patch and stromal regeneration tissue were confirmed by AS-OCT, and glue patch was safely removed. Conclusions and importance: The area of healing tissue beneath the CGP may not be easy to evaluate using the slit-lamp microscopy alone. AS-OCT is a useful tool in the assessment of corneal healing tissue in the presence of cyanoacrylate glue patch.

Detailed phenotypic description of stromal corneal dystrophy in a large pedigree carrying the uncommon TGFBI p.Ala546Asp pathogenic variant.

PURPOSE: The purpose of this study is to describe the corneal clinical spectrum and the intrafamilial phenotypic differences in an extended pedigree suffering from stromal corneal dystrophy due to the rare p.Ala546Asp mutation in TGFBI. METHODS: A total of 15 members from a four-generation Mexican family were ascertained for clinical and genetic assessment. All individuals underwent slit-lamp biomicroscopic examination and an extensive ophthalmological examination including corneal topography (OCULUS Pentacam® AXL), corneal biomechanics (OCULUS Corvis ST), and corneal confocal biomicroscopy (Heidelberg Engineering®). A total of 10 individuals carried the heterozygous c.1637C>A (p. Ala546Asp) mutation at TGFBI exon 12. RESULTS: Nine out of 10 mutation positive patients were available for clinical characterization. The mean age was 35.5 years, with the youngest and the eldest ones being 3 years old and 62 years old, respectively. The median age of onset of the symptoms was 19.7 years. Five (55.6%) patients presented with a predominantly granular corneal dystrophy type 2 (GCD2) phenotype, one presented with a lattice corneal dystrophy (LCD) phenotype, and one with a granular corneal dystrophy type 1 (GCD1) phenotype. Interestingly, two mutation positive subjects had no clinical deposits in the cornea, demonstrating incomplete penetrance of the disorder in this family. CONCLUSIONS: Clinical differences in corneal phenotypes within this CD family and with other pedigrees carrying the same TGFBI genetic defect could be explained by the age of clinical examination of individual patients and/or by the presence of genetic and/or environmental modifiers.

Visual and Refractive Outcomes Following SMILE to Correct Myopia Performed by Surgeons in Training.

PURPOSE: To assess visual outcomes and complications following small incision lenticule extraction (SMILE) performed by cornea fellows under the supervision of experienced surgeons. METHODS: This retrospective, noncomparative case series was designed to assess outcomes following SMILE procedures performed at a large surgical center by cornea fellows between May 1, 2012 and March 30, 2015. Preoperative and postoperative uncorrected distance visual acuity (UDVA), preoperative and postoperative corrected distance visual acuity (CDVA), spherical equivalent (SE) up to -10.00 diopters (D), and complications were recorded. RESULTS: A total of 114 patients (228 eyes) met the inclusion criteria. The mean preoperative SE was -5.79 ± 1.95 D (range: -1.75 to -10.00 D) and the mean cylinder was -2.21 ± 1.43 D (range: 0.00 to -5.50 D). At the last follow-up visit (average: 6.4 months), 94% of the patients achieved a UDVA of 20/30 or better and 96% of the patients achieved stability in their vision. Adverse events were encountered in 40 eyes (17.5%), with epithelial defect being the most common. Two patients required a second intervention to improve visual outcomes. CONCLUSIONS: SMILE performed by cornea fellows under the supervision of an experienced surgeon is an effective and safe refractive procedure with a short learning curve and excellent visual outcomes. [J Refract Surg. 2022;38(1):28-34.].

Visual rehabilitation with limbal autologous stem cells transplant and cataract surgery in a patient with ocular surface squamous neoplasia.

PURPOSE: To describe the outcome of simple limbal epithelial transplantation along with Phacoemulsification and IOL implantation for visual rehabilitation in limbal stem cell deficiency due to ocular surface squamous neoplasia. OBSERVATIONS: This case report of a 66-year-old woman clinically diagnosed with OSSN in her right eye involving all cornea and limbus meridians. Topical chemotherapy for tumor treatment was done, followed by SLET and sequential cataract surgery. The entire tumor could be clinically reduced with topical chemotherapy but a LSCD could not be avoided. After SLET, corneal transparency was restored, and anterior segment details could be seen, phacoemulsification was performed uneventfully. After a follow-up period of 18 months, stable ocular surface and visual acuity and no tumor recurrence was observed. CONCLUSIONS: SLET is an option to restore not only corneal epithelium homeostasis but also gain cornea transparency, avoid keratoplasties and allow anterior segment surgeries to be performed. IMPORTANCE: This case report provide evidence of benefits of simple limbal epithelial transplantation in ocular surface squamous neoplasia and shows that cataract surgery could be performed uneventfully after limbal stem cell transplantation.

Combined Bacterial and Herpes Simplex Virus Keratitis following Small-Incision Lenticule Extraction for the Correction of Myopia.

A 28-year-old male presented unilateral visual loss, intense ocular pain, redness and intraocular hypertension in his right eye 2 days after undergoing small-incision lenticule extraction (SMILE) in both eyes. Initial examination of the affected eye revealed the presence of white infiltrates within the corneal interface, as well as a central epithelial defect. The patient was diagnosed with infectious keratitis, posteriorly the eye was irrigated with balanced saline solution and treatment was initiated with hourly moxifloxacin 0.5%. Since this approach failed to resolve symptoms, a sample from the interface was obtained for PCR assay, which revealed the presence of herpes simplex virus DNA, confirming the cause of the infection. The patient was prescribed a regimen of oral acyclovir, topical ganciclovir and prednisolone. Clinical improvement following resolution of the epithelial defect was observed. Although rare, herpetic keratitis following SMILE is best managed via early diagnosis and initiation of appropriate anti-herpetic treatment.

Cool Crosslinking: Riboflavin at 4°C for Pain Management After Crosslinking for Keratoconus Patients, A Randomized Clinical Trial.

PURPOSE: To explore corneal cooling as a method of pain management in corneal-accelerated collagen cross-linking. METHODS: This was a prospective and interventional randomized clinical trial registered in the National Institutes of Health Clinical Trials through the identifier NCT030760770. The research was conducted at the Institute of Ophthalmology "Conde de Valenciana." A total of 98 patients were randomly assigned to one of the following 2 groups: cold riboflavin (4°C) group or control group (riboflavin at room temperature). The inclusion criteria were patients of any sex, older than 18 years of age with keratoconus diagnosis who needed management with cross-linking in both eyes because of the evidence of progression. The exclusion criteria were patients who had cross-linking without epithelial debridement, unilateral cross-linking, or any other ocular pathologies besides keratoconus and any cognitive incapacity that would make the understanding of the pain test difficult. The main outcome measures were pain, tearing, photophobia, foreign body sensation, and irritation. RESULTS: At 2 hours post-op, pain in the case and control groups was 3.80 ± 3.00 and 8.08 ± 2.21 (P < 0.05), tearing was 1.56 ± 1.96 and 8.29 ± 2.42 (P < 0.05), photophobia was 5.44 ± 3.57 and 7.83 ± 2.64 (P < 0.05), foreign body sensation was 2.20 ± 2.78 and 6.54 ± 2.73 (P < 0.05), and irritation was 3.48 ± 2.98 and 6.79 ± 3.00 (P < 0.05), respectively. A statistical significant difference was maintained in pain values on day 1 (2.79 ± 3.09 and 4.91 ± 3.27 [P < 0.05]), 2 (2.54 ± 2.41 and 4.00 ± 2.43 [P < 0.05]), and 4 (0.45 ± 0.76 and 1.22 ± 1.67 [P < 0.05]). CONCLUSIONS: This study demonstrated that pain and associated symptoms decreased significantly in the riboflavin 4°C group.

Giant Ocular Lipodermoid Cyst in Encephalocraniocutaneous Lipomatosis: Surgical Treatment and Genetic Analysis.

BACKGROUND Encephalocraniocutaneous lipomatosis is a rare neurocutaneous disorder characterized by cutaneous, ocular, and central nervous system anomalies; its molecular etiology was recently identified. This report describes the surgical treatment and genetic characterization of a giant ocular lipodermoid cyst secondary to encephalocraniocutaneous lipomatosis. CASE REPORT An 11-year-old girl with past medical history of absence seizures presented with a reddish protruding mass in her right eye involving the temporal conjunctiva and the peripheral temporal cornea; eyelid closure was not possible due to mass protrusion. She also presented skin tags at the level of the external canthus and 3 alopecic areas at the level of the scalp compatible with nevus psiloliparus. No family history was reported. A dermoid cyst was suspected and excisional biopsy was performed under general anesthesia. A large conjunctival and lamellar corneoscleral resection was done, followed by a corneal tectonic graft. Molecular analysis was carried out, including PCR and Sanger sequencing on DNA obtained from the mass. After surgery, the patient achieved complete eyelid closure, reduction of ocular surface symptoms, and improved aesthetic appearance. Histological analysis confirmed a lipodermoid cyst; genetic tests confirmed a mosaic activating mutation in FGFR1 (c.1638C>A, p.Asn546Lys). The diagnosis was encephalocraniocutaneous lipomatosis. CONCLUSIONS ECCL is a rare condition; an accurate diagnosis comprising clinical and genetic aspects can facilitate the monitoring of possible complications, improve the multidisciplinary treatment, and provide valuable information for future therapy developments. In this case, the patient's quality of life improved significantly, ocular symptoms disappeared, and a good esthetic appearance was achieved.

Practice Patterns in the Management of Primary Pterygium: A Survey Study.

PURPOSE: To characterize cornea specialists' current practice preferences in the management of primary pterygium. METHODS: A 25-item survey regarding indications for surgery, surgical technique, use of adjuvant therapy, type and duration of postoperative therapy, and treatment of early recurrences was designed and sent to members of the Cornea Society through the kera-net listserv. RESULTS: In total, 199 cornea specialists completed the questionnaire. More than 90% considered that surgery should be performed when there is proximity of the pterygium to the visual axis, pain or redness, eye movement restriction, or induction of astigmatism. Cosmesis was considered as an indication by 41.7% of the participants. The most frequent technique for pterygium excision was complete resection including the base and a moderate quantity of Tenon capsule followed by autologous conjunctival or limbal-conjunctival graft. The preferred graft fixation method in this survey was fibrin glue (61.2%). Most respondents reported a recurrence rate of less than 5% and no use of adjuvant agents to prevent recurrence. When early recurrence did occur, the preferred agents were corticosteroids. CONCLUSIONS: This study reflects the preferences of cornea experts regarding primary pterygium treatment and may serve as a guide for the management of this pathology.