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.

Ophthalmic findings in patients with autosomal recessive lamellar ichthyosis due to TGM1 mutations in an isolated population.

PURPOSE: To describe the ocular clinical characteristics of a group of Mexican patients with lamellar ichthyosis (LI) arising from TGM1 pathogenic variants. METHODS: Ophthalmological exploration, pedigree analysis and genetic screening were performed in patients with an established clinical diagnosis of lamellar ichthyosis from families located in a small community in the Southeast of Mexico. RESULTS: Nine patients with LI in five families were identified. There were six affected females. All patients (9/9) demonstrated eye lid abnormalities with eight patients showing lid margin abnormalities. Madarosis was present in only three individuals and corneal scarring was documented in two. All nine individuals carried biallelic TGM1 variants, either homozygously or as compound heterozygous. CONCLUSION: Ocular anomalies are common in individuals with TGM1-related LI. The occurrence of a variety of private or rare mutations hampers the identification of a genotype-phenotype correlation for ocular anomalies in this disorder.

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.

Subconjunctival Sirolimus-Loaded Liposomes for the Treatment of Moderate-to-Severe Dry Eye Disease.

Purpose: To determine the effectiveness of subconjunctival application of a novel sirolimus liposomal formulation for the treatment of dry eye. Methods: A randomized, triple-blind, Phase II clinical trial. Thirty-eight eyes of 19 patients were included. Nine patients (18 eyes) assigned to the sham group (Sham) and 10 patients (20 eyes) to sirolimus-loaded liposomes group (Sirolimus). The treatment group received three doses of subconjunctival liposome-encapsulated sirolimus and the sham group received three doses of liposomal suspension without sirolimus. Subjective (Ocular Surface Disease Index, OSDI) and measured (corrected distance visual acuity, conjunctival hyperemia, tear osmolarity, Schirmer's test, corneal/conjunctival staining and matrix metalloproteinase-9) variables were measured. Results: Sirolimus-entrapped liposomes-treated group OSDI scores changed from 62.19 (± 6.07) to 37.8 (± 17.81) (p=0.0024), and conjunctival hyperemia from 2.0 (± 0.68) to 0.83 (± 0.61) (p<0.0001); Sham group with OSDI scores from 60.02 (± 14.2) to 36.02 (± 20.70) (p=0.01), and conjunctival hyperemia from 1.33 (± 0.68) to 0.94 (± 0.87) (p=0.048). All the other evaluated outcomes only showed significant differences in the sirolimus group: corneal/conjunctival staining score (p=0.0015), lipid layer interferometry (p=0.006), and inferior meibomian gland dropout (p=0.038). No local or systemic adverse effects regarding the medication itself were reported, and the administration route was well accepted. Conclusion: Our findings suggest that sub-conjunctival sirolimus-loaded liposomes are effective in reducing both signs and symptoms of dry eye in patients with poorly controlled moderate-to-severe DED, while avoiding other topical administration adverse effects. Further investigation with a larger sample size is required to determine long-term effects.

Results of one decade of optical keratoplasty in pediatric patients.

BACKGROUND: Keratoplasty in the pediatric population has been considered a high-risk procedure. OBJECTIVE: To know the demographic data of patients younger than 18 years treated with optical keratoplasty, indications for surgery and its results. MATERIAL AND METHODS: A retrospective study was carried out at Conde de Valenciana Ophthalmology Institute, in which the medical records of patients younger than 18 years treated with optical keratoplasty from 2009 to 2019 were analyzed. RESULTS: A total of 53 eyes were included. The most common diagnosis and procedure were keratoconus and penetrating keratoplasty, respectively. Mean initial visual acuity was 2.05 ± 0.99 logMAR, and 0.82 ± 1.33 at last visit. Survival time was 130.34 months. Four failures were recorded. As for associated surgeries, corneal wound closure was recorded in seven eyes prior to transplant; during the keratoplasty procedure, anterior vitrectomy in two eyes, and after the transplant, Ahmed valve implantation and re-suture. A total of eight eyes had glaucoma, five of them diagnosed prior to transplantation. Regarding rejection, 15 eyes had an episode during follow-up, and mean time to transplant rejection was 10.8 months. CONCLUSION: Prolonged graft survival can be achieved with better knowledge and management of different associated factors.

ANTECEDENTES: La queratoplastia en población pediátrica ha sido considerada un procedimiento de alto riesgo. OBJETIVO: Conocer datos demográficos de pacientes menores de 18 años tratados con queratoplastia óptica, indicaciones de la cirugía y sus resultados. MATERIAL Y MÉTODOS: Se realizó un estudio retrospectivo en el Instituto de Oftalmología Conde de Valenciana, en el que se revisaron expedientes de pacientes menores de 18 años tratados con queratoplastia óptica de 2009 a 2019. RESULTADOS: Un total de 53 ojos fueron incluidos. El diagnóstico y el procedimiento más comunes fueron el queratocono y la queratoplastia penetrante. El promedio de agudeza visual inicial fue de 2.05 ± 0.99 logMAR y en la última visita, 0.82 ± 1.33. El tiempo de supervivencia del injerto fue de 130.34 meses. Se registraron cuatro fallas. En cuanto a las cirugías asociadas, antes del trasplante se registró cierre de herida corneal en siete ojos y durante la queratoplastia, vitrectomía anterior en dos ojos y después del trasplante, implante de válvula de Ahmed y resutura. Un total de ocho ojos tuvieron glaucoma, cinco con diagnóstico antes del trasplante. Respecto al rechazo, 15 ojos tuvieron un episodio durante el seguimiento y el tiempo promedio de rechazo al trasplante fue de 10.8 meses. CONCLUSIÓN: Se puede lograr una supervivencia prolongada del injerto con el mejor conocimiento y manejo de los diferentes factores asociados.

Resultados de una década de queratoplastia óptica en pacientes pediátricos / Results of one decade of optical keratoplasty in pediatric patients

Resumen Antecedentes: La queratoplastia en población pediátrica ha sido considerada un procedimiento de alto riesgo. Objetivo: Conocer datos demográficos de pacientes menores de 18 años tratados con queratoplastia óptica, indicaciones de la cirugía y sus resultados. Material y métodos: Se realizó un estudio retrospectivo en el Instituto de Oftalmología Conde de Valenciana, en el que se revisaron expedientes de pacientes menores de 18 años tratados con queratoplastia óptica de 2009 a 2019. Resultados: Un total de 53 ojos fueron incluidos. El diagnóstico y el procedimiento más comunes fueron el queratocono y la queratoplastia penetrante. El promedio de agudeza visual inicial fue de 2.05 ± 0.99 logMAR y en la última visita, 0.82 ± 1.33. El tiempo de supervivencia del injerto fue de 130.34 meses. Se registraron cuatro fallas. En cuanto a las cirugías asociadas, antes del trasplante se registró cierre de herida corneal en siete ojos y durante la queratoplastia, vitrectomía anterior en dos ojos y después del trasplante, implante de válvula de Ahmed y resutura. Un total de ocho ojos tuvieron glaucoma, cinco con diagnóstico antes del trasplante. Respecto al rechazo, 15 ojos tuvieron un episodio durante el seguimiento y el tiempo promedio de rechazo al trasplante fue de 10.8 meses. Conclusión: Se puede lograr una supervivencia prolongada del injerto con el mejor conocimiento y manejo de los diferentes factores asociados.

Abstract Background: Keratoplasty in the pediatric population has been considered a high-risk procedure. Objective: To know the demographic data of patients younger than 18 years treated with optical keratoplasty, indications for surgery and its results. Material and methods: A retrospective study was carried out at Conde de Valenciana Ophthalmology Institute, in which the medical records of patients younger than 18 years treated with optical keratoplasty from 2009 to 2019 were analyzed. Results: A total of 53 eyes were included. The most common diagnosis and procedure were keratoconus and penetrating keratoplasty, respectively. Mean initial visual acuity was 2.05 ± 0.99 logMAR, and 0.82 ± 1.33 at last visit. Survival time was 130.34 months. Four failures were recorded. As for associated surgeries, corneal wound closure was recorded in seven eyes prior to transplant; during the keratoplasty procedure, anterior vitrectomy in two eyes, and after the transplant, Ahmed valve implantation and re-suture. A total of eight eyes had glaucoma, five of them diagnosed prior to transplantation. Regarding rejection, 15 eyes had an episode during follow-up, and mean time to transplant rejection was 10.8 months. Conclusion: Prolonged graft survival can be achieved with better knowledge and management of different associated factors.

Paraproteinemic Keratopathy in a Patient With Previous LASIK Procedure Mimicking Lattice Corneal Dystrophy.

PURPOSE: The aim of this study was to report a unique clinical presentation of paraproteinemic keratopathy after a myopic uneventful laser in situ keratomileusis (LASIK) procedure that led to the diagnosis of gammopathy of undetermined significance. METHODS: This was an interventional case report. A 55-year-old woman present with bilateral branching opacities limited to the optical zone of myopic LASIK. The patient's medical history was unremarkable. RESULTS: After ruling out a mutation in TGF-ß1 , a systemic workup was performed, revealing an IgG level of 12.8 mg/dL, lambda-free light chain of 12.8 mg/dL, and M-spike of 0.6 g/dL. Bone marrow aspiration was slightly hypercellular, without evidence of neoplastic infiltration by plasma cells. The patient underwent 3 cycles of systemic chemotherapy, with improvement in best-corrected visual acuity. CONCLUSIONS: Paraproteinemic keratopathy is a rare clinical presentation that may lead to a systemic diagnosis of hematologic malignancy. To the best of our knowledge, this is the first reported case of paraproteinemic keratopathy after LASIK.

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.

Belisario Domínguez: A life and death deserving of a medal.

Belisario Domínguez was a Mexican physician, ophthalmologist, and politician. He traveled abroad to France, where he studied High School, later he entered the School of Medicine at Sorbonne University in Paris. Back in Mexico, Domínguez installed his medical office in his house. Belisario was recognized for his philanthropic attitude, he also often sought the well-being being of Chiapas and Mexico. In 1911 he became Comitán Municipal President, after the overthrown of presidente Porfirio Díaz.He witnessed the coup against President Francisco Madero by General Huerta. Belisario wrote a speech in which he expressed the shame of having a traitor and murderer as President. As consequence of the speech, he was killed. After Belisario's assassination, an outrage was incited, damaging the image of President Huerta. Belisario's civic value was honored with a medal that bears his name " Belisario Domínguez Medal" in 1953 which is the greatest recognition that can be obtained by a Mexican.

A novel homozygous ZNF469 variant causing brittle cornea syndrome is associated with corneal ectasias in heterozygous carriers.

AIM: To describe a family segregating a novel truncating ZNF469 homozygous mutation causing brittle cornea syndrome type 1 in a male patient and associated with corneal ectasia in his two heterozygous young children. METHODS: A 49-year-old affected male and his 12- and 8-year-old, apparently healthy, siblings underwent phenotypic and genetic assessment. An Oculus Pentacam Scheimpflug topographer system was employed for keratometries and central corneal thickness measurements. Exome sequencing was performed in DNA from the index case with subsequent Sanger sequencing confirmation of the ZNF469 gene causal variant in his relatives. RESULTS: The index case had a history of bilateral keratoglobus, corneal perforations, bilateral hypoacusia, and skeletal anomalies. His two children exhibited topographic anomalies compatible with keratoconus suspects as well as mild skeletal anomalies. Genetic analysis identified a novel homozygous c.2340delC variant in the ZNF469 gene, which predicts a p.(Arg781Glufs*19) truncated protein. Sanger sequencing identified heterozygosity for the c.2340delC variant in DNA from both siblings. CONCLUSION: Our results expand the mutational spectrum associated with brittle cornea syndrome and provide the first demonstration of early corneal anomalies in subjects carrying monoallelic ZNF469 variants.

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.

Reliability, repeatability, and accordance between three different corneal diagnostic imaging devices for evaluating the ocular surface.

Purpose: To evaluate repeatability, reproducibility, and accordance between ocular surface measurements within three different imaging devices. Methods: We performed an observational study on 66 healthy eyes. Tear meniscus height, non-invasive tear break-up time (NITBUT) and meibography were measured using three corneal imaging devices: Keratograph 5M (Oculus, Wetzlar, Germany), Antares (Lumenis, Sidney, Australia), and LacryDiag (Quantel Medical, Cournon d'Auvergne, France). One-way ANOVAs with post hoc analyses were used to calculate accordance between the tear meniscus and NITBUT. Reproducibility was assessed through coefficients of variation and repeatability with intraclass correlation coefficients (ICC). Reliability of meibography classification was analyzed by calculating Fleiss' Kappa Index and presented in Venn diagrams. Results: Coefficients of variation were high and differed greatly depending on the device and measurement. ICCs showed moderate reliability of NITBUT and tear meniscus height measurements. We observed discordance between measurements of tear meniscus height between the three devices, F2, 195 = 15.24, p < 0.01. Measurements performed with Antares were higher; 0.365 ± 0.0851, than those with Keratograph 5M and LacryDiag; 0.293 ± 0.0790 and 0.306 ± 0.0731. NITBUT also showed discordance between devices, F2, 111 = 13.152, p < 0.01. Measurements performed with LacryDiag were lower (10.4 ± 1.82) compared to those of Keratograph 5M (12.6 ± 4.01) and Antares (12.6 ± 4.21). Fleiss' Kappa showed a value of -0.00487 for upper lid and 0.128 for inferior lid Meibography classification, suggesting discrete to poor agreement between measurements. Conclusion: Depending on the device used and parameter analyzed, measurements varied between each other, showing a difference in image processing.