Macular corneal dystrophy with iridofundal coloboma in the same patient: a unique combination.

A young a presented with painless, progressive diminution of vision in both eyes (BE). Slit lamp examination revealed the presence of a single central corneal opacity in the right eye and multiple corneal opacities of varying sizes in the left eye (LE), limited to the anterior-mid corneal stroma. Microcornea with reduced central corneal thickness and complete inferonasal iris coloboma along with inferior fundal coloboma, sparing both the disc and macula, were noted in BE. A diagnosis of BE macular corneal dystrophy (MCD) and iridofundal coloboma (IFC) was made. The patient underwent LE sutureless anterior lamellar therapeutic keratoplasty. On histopathological examination, the excised corneal tissue revealed stromal lamellar disarray with positive colloidal iron staining, strongly suggestive of MCD. Whole-exome sequencing revealed the presence of a likely pathogenic carbohydrate sulfotransferase 6 (CHST6) mutation, confirming the diagnosis of MCD. This concurrent presence of IFC with a corneal stromal dystrophy is previously unreported in the literature, to the best of our knowledge.

Corneal Sensitivity Is Inversely Correlated With Severity of Diabetic Retinopathy in a Predominantly Underrepresented Population.

PURPOSE: To assess the relationship between diabetic retinopathy (DR) and corneal sensitivity. METHODS: In this prospective study, 100 eyes of 50 patients from primarily underrepresented racial and ethnic backgrounds with DR underwent assessment of corneal sensitivity using a Cochet-Bonnet esthesiometer. Severity of DR was graded by a masked reading center. Corneal sensitivity was compared in eyes with current or regressed proliferative DR (PDR) (n=35) and eyes with nonproliferative DR (NPDR) with no history of PDR (n=65). Corneal sensitivity in eyes that regressed from PDR to NPDR with anti-vascular endothelial growth factor (anti-VEGF) therapy (n=7) was compared to treatment-naïve eyes with no current or prior PDR (n=55) and to eyes with newly diagnosed, treatment-naïve PDR (n=12). RESULTS: In eyes with current or prior PDR, the median corneal sensitivity (average of 4 quadrants) was 0.5 cm (interquartile range [IQR] 0-3.375), whereas in eyes with no current or prior PDR, the median corneal sensitivity was 4.75 cm (IQR 2.0-6.0, P < .0001). The median corneal sensitivity in eyes with regressed PDR was 0 cm (IQR 0-0.875), significantly lower than eyes with no current or prior PDR (4.5 cm, IQR 4.0, P = .0076) and no different than eyes with untreated PDR (0 cm, IQR 1.25). The odds of eyes with DR severity scale score ≥60 having complete corneal sensitivity loss was 3.6 times that of eyes with NPDR. CONCLUSIONS: Corneal sensitivity is impaired in eyes with PDR compared to NPDR and is not rescued by anti-VEGF therapy. Assessment of corneal sensitivity in eyes with DR may identify patients at risk for additional complications, including neurotrophic keratopathy. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Safety and Efficacy of the Phototherapeutic Keratectomy for Treatment of Recurrent Corneal Erosions: A Systematic Review and Meta-Analysis.

BACKGROUND: Phototherapeutic keratectomy (PTK) has been increasingly used to treat severe recurrent corneal erosion syndrome (RCES) patients who do not respond to other treatments. However, the efficacy and complication of each study are currently uncertain due to varying rates. OBJECTIVES: The objective of this study was to investigate the safety and efficacy of the PTK for recurrent corneal erosions. METHODS: This article performed a systematic literature research in Cochrane, Embase, PubMed, Scopus, and the Web of Science for the literature on PTK treatment of RCES until December 20, 2022. The extracted data including recurrence rate and the adverse event rate were used for meta-analysis. RESULTS: The recurrence rate was 18% (95% CI, 13%-24%) (129/700 eyes). Subgroup analysis showed that the RCE recurrence was 17% (95% CI, 9%-24%) after trauma and 22% (95% CI, 11%-32%) in the corneal dystrophy group. Treatment-related adverse events included subepithelial haze, hyperopic shift, and decrease of the best spectacle-corrected visual acuity. In this study, the incidence of these events was 13% (95% CI, 6%-21%), 20% (95% CI, 11%-28%), and 11% (95% CI, 5%-16%), respectively. CONCLUSIONS: PTK represented a valuable treatment option for patients with recurrent corneal erosions, especially those with traumatic injuries, which had minimal side effects.

[Corneal disease in childhood-Hereditary, degenerative or infectious?] / Hornhauterkrankungen im Kindesalter ­ Hereditär, degenerativ oder infektiös?

BACKGROUND: Adequate visual acuity significantly contributes to the age-appropriate development of children's neurobehavior. Infantile corneal opacities are rare but implicate a high potential for amblyopia. OBJECTIVE: This review aims to provide an overview of the most common causes of infantile corneal opacities and highlights ophthalmopathological correlations. METHODS: The following review is based on an extensive literature search. RESULTS: If metabolic diseases, traumatic or infectious events can be excluded as a cause for an infantile corneal opacity, it is important to focus on the 3Ds, corneal dysgenesis, corneal dystrophy or corneal degeneration. DISCUSSION: If corneal opacities occur in childhood, early recognition, diagnosis, and initiation of treatment, including prophylaxis of amblyopia, are of utmost importance. In unexplained corneal opacities the histopathological work-up of the explanted cornea can contribute to the final diagnosis.

[Epithelial basement membrane corneal dystrophy: A case report]. / Distrofia de membrana basal epitelial corneal: a propósito de un caso.

Epithelial basement membrane corneal dystrophy is a rare entity, characterized by recurrent corneal erosions secondary to a disorder in the attachment of the corneal epithelium to the basement membrane. To date, mainly the ophthalmological aspect of cases has been reported, with little emphasis on the pathology of this lesion. Here we aim to describe the microscopy and discuss the clinical and therapeutic aspects of a case.

[Ocular alterations in patients with Alport syndrome-An update]. / Okuläre Veränderungen bei Patienten mit Alport-Syndrom ­ ein Update.

BACKGROUND AND OBJECTIVE: Alport syndrome (AS) is a rare hereditary systemic disease that results in alterations of the kidneys, inner ear, and various structures of the eye. It is caused by mutations in one of the genes encoding collagen type IV. In recent years, new and innovative imaging techniques have added characteristics of ocular alterations in AS and provided new insights, including into the pathogenesis of the disease. The aim of this paper is to provide an overview of the current knowledge of ocular changes in AS, as well as to present the Alport ocular pass. METHOD: Narrative review article. RESULTS: Ocular manifestations of AS include changes in the cornea, lens, and retina. Specifically, posterior polymorphic corneal dystrophy, anterior lenticonus (pathognomonic for AS), and various retinal changes have been described, which have been further characterized in recent years by newer imaging techniques. In particular, foveal changes in AS may present as both a thickened central retina in the context of foveal hypoplasia or a staircase-like thinning of the fovea. Both lesions could provide further insights into the role of type IV collagen in ocular structures. CONCLUSION: The AS can manifest in various structures of the eye. The staircase-like changes of the central retina in AS patients indicate the important role of collagen type IV in the homeostasis and regular function of the inner retinal layers. The often mild foveal hypoplasia may provide clues to the role of collagen type IV in retinal embryogenesis. While anterior lenticonus is pathognomonic for AS and can be treated easily by refractive lens exchange, the only option currently available for retinal alterations is close follow-up and, if necessary, treatment of systemic complications of AS.

Clinical and electrophysiological findings of facial palsy in a case of hereditary gelsolin amyloidosis.

Hereditary gelsolin amyloidosis (HGA) is an autosomal dominant systemic amyloidosis, characterized by cranial and sensory peripheral neuropathy, corneal lattice dystrophy, and cutis laxa. We report a case of HGA presenting with bilateral facial palsy. A 70-year-old Japanese man presented with slowly progressive bilateral facial palsy and facial twitching, which had started in his 40s. His mother also had the same symptoms due to an unknown cause but rest of the family did not. He showed incomplete facial palsy with no frontal muscle movement and partial movement of the orbicularis oris and orbicularis oculi muscles. The patient showed no synkinesis. Electroneurography revealed symmetric low compound motor action potential amplitude of the orbicularis oris muscle, and a nerve excitability test showed a symmetric increase in the response threshold. Despite the partial voluntary movement of the orbicularis oculi muscle, bilateral blink reflexes were absent. He also showed facial spasms after contraction of the orbicularis oris muscle. Genetic testing revealed a heterozygous c.640G>A mutation (p. Asp214Asn); therefore, the patient was diagnosed with HGA. HGA related facial palsy showed moderate bilateral, upper blanch-dominant axonal degeneration of the facial nerve without reinnervation, and trigeminal nerve neuropathy.

Infectious Crystalline Keratopathy Secondary to Mycobacterium chelonae.

PURPOSE: The aim of this study was to describe the clinical presentation and multimodal imaging of a patient diagnosed with infectious crystalline keratitis (ICK) secondary to Mycobacterium chelonae . METHODS: This is a case report of a patient with a crystalline corneal infiltrate imaged with anterior segment optical coherence tomography and in vivo scanning laser confocal microscopy. Bacterial, fungal, acanthamoeba, and acid-fast cultures were performed to identify the causal pathogen. RESULTS: Examination revealed a white stellate opacity in the midstroma underlying the scalloped border of an area of central corneal stromal thinning, consistent with a diagnosis of ICK. Anterior segment optical coherence tomography demonstrated a hyperreflective diamond-shaped opacity located at a depth of 334 µm, which demonstrated multiple stellate projections on in vivo scanning laser confocal microscopy. The acid-fast culture was positive for Mycobacterium chelonae . CONCLUSIONS: Although ICK is most commonly associated with Streptococcus species, it may be secondary to atypical bacteria including Mycobacterium species, underscoring the importance of diagnostic imaging and collecting corneal cultures to identify the pathogenic organism.

Detection of Secondary Corneal Lactoferrin Amyloidosis Based on Histologic Biopsies Combined with Mass Spectrometry: A Case Report.

Amyloidosis is characterized by systemic or local deposition of amyloid fibrils outside organs and tissues. Amyloidosis is rarely seen on cornea. A 30-year-old woman patient had had trichiasis in both eyes for 8 years. Trichiasis was observed, which touched the cornea. Slit lamp microscopy showed white gelatinous droplet-like eminences and trichiasis in the lower cornea of the right eye. Optical coherence tomography showed that the lesion involved most of the cornea. Hematoxylin and eosin staining showed that most of the stroma stained red, with scattered inflammatory cells. High expression of lactoferrin was detected by mass spectrometry, and the case was diagnosed as secondary corneal lactoferrin amyloidosis in the right eye.

Prevalence of neurotrophic keratopathy in patients with chronic ocular graft-versus-host disease.

PURPOSE: To determine the prevalence, clinical characteristics, and risk factors associated with neurotrophic keratopathy (NK) in patients with chronic ocular graft-versus-host disease (oGVHD). DESIGN: Retrospective cohort study. METHODS: We performed a chart review of patients diagnosed with chronic oGVHD between January 2015 and December 2018 at a single academic institution and recorded demographic data, systemic and ocular comorbidities, history of hematologic malignancy, transplant characteristics, oGVHD severity scores, and adnexal and ocular examination findings. We determined the prevalence of NK and clinical characteristics associated with NK in these patients. A multivariate logistic regression analysis was performed to determine the risk factors associated with NK in these patients. MAIN OUTCOME MEASURE: Prevalence of NK in chronic oGVHD. RESULTS: We identified 213 patients diagnosed with chronic oGVHD following hematopoietic stem cell or bone marrow transplantation from our electronic patient database, and the prevalence of NK was 14%. The mean age of oGVHD patients with NK was 62.6 ± 12.9 years; 48% were women, 19 had unilateral NK, and ten had bilateral NK. In the cohort, 56%, 20%, and 24% eyes of the patients had grades 1, 2, and 3 of NK, respectively. The mean time to diagnose NK after transplantation was 52.9 ± 45.4 months. oGVHD patients diagnosed with NK had a significantly higher NIH oGVHD severity score (p = 0.04) and a lower corneal sensation score (p = 0.0001) than those without NK. Our analyses showed a significantly higher CFS score (p = 0.01) and a trend toward lower Schirmer test scores (p = 0.16) and tear break-up times (p = 0.08) in oGVHD patients with NK. Additionally, we observed a significantly higher prevalence of persistent epithelial defect (p = 0.0001), corneal ulceration (p = 0.0001), and corneal perforation (p = 0.005) in oGVHD patients diagnosed with NK. A logistic regression analysis to determine factors associated with NK showed that a higher NIH oGVHD score (odds ratio [OR] = 2.03, p = 0.026) and history of cataract surgery (odds ratio [OR] = 5.03, p = 0.001) are significant risk factors for NK in oGVHD patients. CONCLUSIONS: The prevalence of NK in chronic oGVHD patients was 14% during the study period. Our analysis shows that oGVHD patients with a higher NIH oGVHD severity score and previous history of cataract surgery are at a higher risk of developing NK and may develop severe sequelae such as persistent epithelial defect or corneal ulceration.

Neurotrophic Keratopathy After Herpes Zoster Ophthalmicus.

PURPOSE: The aim of this study was to describe risk factors for neurotrophic keratopathy (NK) after herpes zoster ophthalmicus (HZO). METHODS: This study was a retrospective review of all patients seen at the Auckland District Health Board with HZO from 2006 through 2016. Cox proportional hazards analysis was performed to examine time to development of neurotrophic keratitis. RESULTS: Eight hundred sixty-nine patients were included in the study with a median follow-up of 6.3 years (5504.4 patient-years). The median age was 65.5 years (interquartile range 52.9-75.4), and 456 subjects (52.5%) were male. NK developed in 58 patients (6.7%), with the highest hazard 1 to 2 years after onset of HZO. On univariate analysis, age, White ethnicity, best-corrected visual acuity (BCVA) at presentation, intraocular pressure, corneal involvement, uveitis, and number of recurrences were associated with increased risk of NK. On multivariate analysis, the following factors were significant: age (hazard ratio [HR] = 1.03; P = 0.021), White ethnicity (HR = 3.18; P = 0.015), BCVA (HR = 1.81; P = 0.026), uveitis (HR = 3.77; P = 0.001), and recurrence (HR = 1.34; P < 0.001). Vision loss (BCVA ≤6/15) was more frequent in subjects with NK (65.5% vs. 16.3%, P < 0.001). CONCLUSIONS: NK is a relatively common and serious complication of HZO and occurs more frequently in older White individuals, those with poor visual acuity at presentation, and those with uveitis. Vision loss occurs in approximately two-thirds of patients.

Corneal Endothelial Transplantation in Uveitis: Incidence and Risk Factors.

PURPOSE: To estimate the incidence of corneal endothelial transplantation (CET) and identify risk factors among patients with noninfectious ocular inflammation. DESIGN: Retrospective cohort study. METHODS: Adult patients attending United States tertiary uveitis care facilities diagnosed with noninfectious ocular inflammation were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Time-to-event analysis was used to estimate the incidence of CET, including penetrating keratoplasty, Descemet stripping endothelial keratoplasty, or Descemet membrane endothelial keratoplasty procedures. The incidence of CET was calculated. Potential risk factors for CET were also evaluated using Cox regression, accounting for correlation between eyes of the same patient. RESULTS: Overall, 14,264 eyes met eligibility criteria for this analysis, with a median follow-up of 1.8 eye-years. The Kaplan-Meier estimated incidence of CET within 10 years was 1.10% (95% CI, 0.68%-1.53%). Risk factors for CET included age >60 years vs <40 years (adjusted hazard ratio [aHR], 16.5; 95% CI, 4.70-57.9), anterior uveitis and scleritis vs other types (aHR, 2.97; 95% CI, 1.46-6.05; and aHR, 4.14; 95% CI,1.28-13.4, respectively), topical corticosteroid treatment (aHR, 2.84; 95% CI, 1.32-6.13), cataract surgery (aHR, 4.44; 95% CI, 1.73-11.4), tube shunt surgery (aHR, 11.9; 95% CI, 5.30-26.8), band keratopathy (aHR, 5.12; 95% CI, 2.34-11.2), and hypotony (aHR, 7.38; 95% CI, 3.14-17.4). Duration of uveitis, trabeculectomy, peripheral anterior synechia, and ocular hypertension had no significant association after multivariate adjustment. CONCLUSIONS: In patients with ocular inflammation, CET occurred infrequently. Tube shunt surgery, hypotony, band keratopathy, cataract surgery, and anterior segment inflammation were associated with increased risk of undergoing CET; these factors likely are associated with endothelial cell damage.

Topical Nerve Growth Factor for the Treatment of Neurotrophic Keratopathy Caused by Wallenberg Syndrome.

PURPOSE: The aim of this study was to report a case of central neurotrophic keratopathy (NK) in Wallenberg syndrome (WS) and its successful management with topical recombinant nerve growth factor (rNGF). METHODS: A 47-year-old man with WS caused by a stroke in the territory of the left vertebrobasilar artery complained of progressive visual loss in his left eye (OS). Examination showed corneal anesthesia associated with a corneal epithelial ulceration consistent with a diagnosis of NK grade 3 of central origin. Topical treatment with rNGF, 1 drop 6 times daily, was started for 8 weeks, and the patient was followed up for 1 year. RESULTS: Topical treatment with rNGF was successful in promoting complete epithelial corneal healing. No recurrence was seen at 1-year follow-up. CONCLUSIONS: Clinicians should be aware that visual loss can also occur from NK of central origin. To the best of our knowledge, this is the first case report of NK caused by WS successfully treated with rNGF reported in the literature.

Diseases of the corneal endothelium.

The corneal endothelial monolayer and associated Descemet's membrane (DM) complex is a unique structure that plays an essential role in corneal function. Endothelial cells are neural crest derived cells that rest on a special extracellular matrix and play a major role in maintaining stromal hydration within a narrow physiologic range necessary for clear vision. A number of diseases affect the endothelial cells and DM complex and can impair corneal function and vision. This review addresses different human corneal endothelial diseases characterized by loss of endothelial function including: Fuchs endothelial corneal dystrophy (FECD), posterior polymorphous corneal dystrophy (PPCD), congenital hereditary endothelial dystrophy (CHED), bullous keratopathy, iridocorneal endothelial (ICE) syndrome, post-traumatic fibrous downgrowth, glaucoma and diabetes mellitus.

Atypical Case of Bilateral Chandler Syndrome With Recurrent Band Keratopathy.

PURPOSE: To report a unique case of bilateral Chandler syndrome with recurrent band keratopathy. METHODS: This is a retrospective observational case report. RESULTS: A 39-year-old Asian man presented with progressive painless diminution of vision in both eyes for 6 years. Examination revealed diffuse corneal edema, hammered silver appearance of endothelium with guttae-like lesions, and corectopia in the right eye and mild corneal edema, central band keratopathy, and guttae-like lesions on the endothelium and peripheral anterior synechiae in the left eye. Routine specular microscopy, confocal microscopy, and pachymetry were performed. A clinical diagnosis of bilateral Chandler syndrome with band keratopathy was made. Superficial epithelial keratectomy with ethylenediaminetetraacetic acid (EDTA) chelation was performed in the left eye first, followed by Descemet-stripping automated endothelial keratoplasty in the right eye. Histopathological examination of the surgically excised Descemet membrane in the right eye showed multilayered endothelium with adhered epithelial cells consistent with Chandler syndrome. At 9-month follow-up, the right eye showed a clear cornea with an attached graft and the left eye revealed recurrence of central band keratopathy for which repeat EDTA chelation was successfully performed. CONCLUSIONS: Recurrent band keratopathy coincident with endothelial dysfunction in iridocorneal endothelial syndrome can be repeatedly treated with EDTA chelation, whereas endothelial keratoplasty might be delayed until the time point of corneal decompensation.

Coexistence of Meesmann Corneal Dystrophy and a Pseudo-Unilateral Lattice Corneal Dystrophy in a Patient With a Novel Pathogenic Variant in the Keratin K3 Gene: A Case Report.

PURPOSE: This study aims to clinically and genetically report a case of coexisting Meesmann corneal dystrophy (MECD) and pseudo-unilateral lattice corneal dystrophy (LCD). METHODS: Clinical characterization was supported by a complete ophthalmological evaluation, including visual acuity measurement and slit-lamp examination. Molecular diagnosis was performed by whole-exome sequencing analyzing the gelsolin, keratin K3 (KRT3), keratin K12, and transforming growth factor-beta-induced genes. RESULTS: A 57-year-old woman presented with recurrent corneal erosions over 17 years and visual impairment in both eyes. Ophthalmological evaluation revealed multiple central tiny cysts in the epithelium of both eyes and lattice linear lesions only in the right cornea. In both eyes, a corneal posterior crocodile shagreen degeneration could also be observed. These findings were compatible with a MECD and a unilateral LCD. Molecular analysis identified the novel heterozygous nucleotide substitution c.1492G>A (amino acid change p.Glu498Lys) in the KRT3 gene, in cosegregation with the MECD familial phenotype. However, no genetic evidence supported the unique LCD phenotype observed in the patient. CONCLUSIONS: To the best of our knowledge, this is the first report of a pseudo-unilateral LCD in a patient with coexistent MECD. Moreover, the genetic analysis showed a novel mutation in the previously MECD-associated gene KRT3.