Variable Phenotype of Congenital Corneal Opacities in Biallelic CYP1B1 Pathogenic Variants.

PURPOSE: The aim of this study is to describe the variable phenotype of congenital corneal opacities occurring in patients with biallelic CYP1B1 pathogenic variants. METHODS: A retrospective chart review was conducted to identify patients with congenital corneal opacities and CYP1B1 pathogenic variants seen at UPMC Children's Hospital of Pittsburgh. Ophthalmic examination, high-frequency ultrasound, anterior segment optical coherence tomography, histopathologic images, and details of genetic testing were reviewed. RESULTS: Three children were identified. All presented with raised intraocular pressure. Two patients showed bilateral limbus-to-limbus avascular corneal opacification that did not resolve with intraocular pressure control; 1 showed unilateral avascular corneal opacity with a crescent of clear cornea, iridocorneal adhesions, iridolenticular adhesions, and classical features of congenital glaucoma in the fellow eye (enlarged corneal diameter, Haab striae, and clearing of the corneal clouding with appropriate intraocular pressure control). The first 2 patients were visually rehabilitated with penetrating keratoplasty. Histopathology revealed distinct features: a variably keratinized epithelium; a thick but discontinuous Bowman-like layer with areas of disruption and abnormal cellularity; Descemet membrane, when observed, showed reduced endothelial cells; and no pathological changes of Haab striae were identified. Two patients had compound heterozygous pathogenic variants in CYP1B1 causing premature stop codons, whereas 1 was homozygous for a pathogenic missense variant. CONCLUSIONS: Congenital corneal opacities seen in biallelic CYP1B1 pathogenic variants have a variable phenotype. One is that commonly termed as Peters anomaly type 1 (with iridocorneal adhesions, with or without iridolenticular adhesions) and the other is a limbus-to-limbus opacity, termed CYP1B1 cytopathy. Clinicians should be aware of this phenotypic variability.

[PETERS ANOMALY AND PETERS PLUS SYNDROME].

INTRODUCTION: Peters anomaly is characterized by a defect in the development of the anterior segment of the eye during fetal development (Anterior segment dysgenesis). This anomaly presents a broad clinical presentation ranging from minimal peripheral corneal opacity to extensive adhesions of the iris and lens with dense central corneal opacity that impairs vision. Peters Plus Syndrome is a recessive autosomal syndrome manifested by Peters anomaly, along with systemic disorders such as brachydactyly (short fingers and toes), short stature, a developmental delay, dysmorphic facial features, and may accompanied with heart and genitourinary malformations. The most common sign of Peters' anomaly is corneal opacity that appears at birth. This opacity can cause blockage of the central visual axis and cause the development of a deprivational amblyopia. In addition, the patient may suffer from glaucoma due to malformations in the angle structures as well as a shallow anterior chamber. Treatments are aimed at clearing the central visual axis as soon as possible in order to allow the visual system to mature and to avoid the development of amblyopia. Full-thickness corneal transplantation combined with Cataract surgery if necessary is the current standard of care. Optical iridoplasty is a milder surgical alternative in cases where the corneal opacity is not significant.

Aesthetic corneal tattooing/keratopigmentation using tattoo pen machine: choosing suitable method and color.

PURPOSE: This article aims to present the corneal tattooing method and how using a tattoo pen machine can improve aesthetic appearance in patients with corneal leukoma. METHODS: In this study, 42 patients were evaluated who had no visual potential and who had undergone colored corneal tattooing using an automatic tattoo pen machine for aesthetic purposes. The procedure was conducted according to the principles of the Declaration of Helsinki. The commercially available tattoo ink that has traditionally been used on human skin (brown, green, and black) for years was used for all the patients in this study, and 252 corneal photographs (with a Topcon slit lamp imaging device at 16 magnifications, i.e., 16 ×) taken within the last 2 years were evaluated retrospectively. Red, green, and blue (RGB) and hue, saturation, and lightness (HSL) values of the tattooed areas, such as pupils and iris, in corneal photographs were determined online using the Color Code Finder program. The RGB and HSL values of the pupil and iris were compared before surgery on the first day and first week, first month, third month, and twelfth month after surgery. RESULTS: In the first postoperative month, the mean pupil lightness (L) and iris L values were found to have increased by 10.7% and 5.7%, respectively. Between the first month and the first year, the L value of the mean pupil and that of the iris increased by 1.7% and 5.2%, respectively. The increase in the RGB value of the mean pupil in the first month was statistically significant (p = 0.02). The highest increase in RGB values of the iris was observed in the first week and first month (p = 0.113). This result shows that the majority of fading occurred in the first month. After the first month, the increase in the L value in the black-colored pupil was less than that in the brown- or green-colored iris. These results show that light colors fade faster and more. CONCLUSION: Esthetically, corneal leukoma causes severe psychological problems. Many patients are unable to use prosthetic contact lenses. Evisceration surgery has many complications, and limbal stem cells are used in evisceration surgery. Corneal tattooing using a tattoo pen machine is an easy, practical, and repeatable method used for aesthetic purposes. Successful results require the use of appropriate methods, ink, and ophthalmologist's experience. All patients in this study had a more aesthetic appearance than the preoperative white eye. Further studies are needed to develop a colored aesthetic tattooing method with a tattoo pen machine.

Mini-Review: Clinical Features and Management of Granular Corneal Dystrophy Type 2.

Granular corneal dystrophy type 2 (GCD2) is an autosomal dominant corneal stromal dystrophy that is caused by p.Arg124His mutation of transforming growth factor ß induced (TGFBI) gene. It is characterized by well demarcated granular shaped opacities in central anterior stroma and as the disease progresses, extrusion of the deposits results in ocular pain due to corneal epithelial erosion. Also, diffuse corneal haze which appears late, causes decrease in visual acuity. The prevalence of GCD2 is high in East Asia including Korea. Homozygous patients show a severe phenotype from an early age, and the heterozygote phenotype varies among patients, depending on several types of compound heterozygous TGFBI mutations. In the initial stage, conservative treatments such as artificial tears, antibiotic eye drops, and bandage contact lenses are used to treat corneal erosion. Different surgical methods are used depending on the depth and extent of the stromal deposits. Phototherapeutic keratectomy removes anterior opacities and is advantageous in terms of its applicability and repeatability. For deeper lesions, deep anterior lamellar keratoplasty can be used as the endothelial layer is not always affected. Recurrence following these treatments are reported within a wide range of rates in different studies due to varying definition of recurrence and follow-up period. In patients who have undergone corneal laser vision-correction surgeries such as photorefractive keratectomy, LASEK, or LASIK including SMILE surgery, corneal opacity exacerbates rapidly with severe deterioration of visual acuity. Further investigations on new treatments of GCD2 are necessary.

Changes in Corneal Clouding Over Time in Patients With Mucopolysaccharidosis.

PURPOSE: Mucopolysaccharidoses (MPSs) are a rare group of lysosomal storage disorders characterized by the accumulation of incompletely degraded glycosaminoglycans (GAGs) in multiple organ systems, including the eye. Visual loss occurs in MPS predominantly due to corneal clouding. Despite the success of enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) in improving many systemic manifestations of MPS, less is known about their effect on corneal clouding. This study prospectively analyses the effect of both ERT and HSCT on corneal clouding using objective measures over time. METHODS: This is a prospective longitudinal observational study. Corneal clouding was assessed in each participant using slitlamp, digital slit-lamp photographs, and an iris camera (Corneal Opacification Measure [COM] and the Pentacam system). RESULTS: Data were collected for 65 participants: 39 MPS I (Hurler), 5 MPS II (Hunter), 12 MPS IV (Morquio), and 9 MPS VI (Maroteaux-Lamy). Follow-up data are available for 45 participants (29 MPS I, 3 MPS II, 6 MPS IV, and 7 MPS VI). CONCLUSIONS: This study found corneal clouding to be stable in most participants with MPS I, II, IV, and VI over a follow-up period of 5 to 75 months (median of 30 months) when measured with clinical corneal grading systems, graded digital slit-lamp images, and iris camera COMs. For those with Pentacam densitometry measures, there was a progression of corneal clouding, on average, in those with MPS I and MPS VI. There was no apparent difference in progression of corneal clouding between patients who were on ERT, HSCT, or no treatment.

Acute central corneal haze and thinning with atypical keratitis presentation.

A 24-year-old woman presented with a 7-day history of blurry vision, redness, and extreme pain in her right eye. She had no pertinent medical or ocular history and did not use spectacles or contacts. Uncorrected distance visual acuity (UDVA) was 20/40 in the right eye and could not be improved with refraction. Slitlamp examination revealed a 1.5 × 1.5 mm central epithelial defect with surrounding white blood cell recruitment. Confocal microscopy (Figure 1JOURNAL/jcrs/04.03/02158034-202304000-00020/figure1/v/2023-03-24T200747Z/r/image-tiff) was performed, and she was treated with chlorhexidine 0.02% drops every hour in the right eye. 2 weeks later, the cornea had completely re-epithelialized; however, persistent corneal haze, decreased visual acuity, and corneal thinning and flattening was noted. Pachymetry was 484 µm in the right eye and UDVA was 20/40 (Supplemental Figure 1, available at http://links.lww.com/JRS/A836). In the following 2 weeks, UDVA improved to 20/25. 6 months after the initial presentation, UDVA was unchanged and faint central corneal haze was noted on examination (Figure 2JOURNAL/jcrs/04.03/02158034-202304000-00020/figure2/v/2023-03-24T200747Z/r/image-tiff). Of interest, her family history is significant for her younger 16-year-old brother with 3 prior episodes of a similar type of keratitis/keratopathy over the course of 2 years in both eyes with similar central paracentral corneal haze, thinning, and flattening and similar confocal findings (Figure 3JOURNAL/jcrs/04.03/02158034-202304000-00020/figure3/v/2023-03-24T200747Z/r/image-tiff). He also was unresponsive to topical antibiotics and antivirals except topical chlorhexidine. Her brother has been our patient for the last several years prior to her first visit to our clinic. What is your diagnosis? What medical diagnostic tests, if any, would you recommend? Is this an infectious or simply an inflammatory response? Is there any genetic or familial predisposition?

Subjective and objective evaluation of corneal haze after accelerated corneal crosslinking for corneal ectasias.

PURPOSE: To evaluate the relationship between subjective (slit lamp examination [SLE]) and objective (densitometry) measurements of corneal haze after accelerated corneal crosslinking (aCXL), assess the relationship between densitometry and corrected distance visual acuity (CDVA), and determine the effect of baseline characteristics on densitometry after aCXL in eyes with progressive keratoconus and other ectasias. SETTING: Kensington Eye Institute and Bochner Eye Institute, Toronto, Canada. DESIGN: Retrospective analysis of a prospective interventional cohort study. METHODS: Scheimpflug-derived corneal densitometry, CDVA, maximum keratometry (Kmax ), and central corneal thickness were measured preoperatively and up to 1 year after aCXL, and post-operative haze was estimated with SLE (n = 483 eyes). A random effect model was used to examine the relationship between post-operative subjective haze with SLE and densitometry. Linear mixed models were used to examine the relationship between densitometry, pre-operative baseline characteristics, and CDVA. RESULTS: There was a significant association between subjective haze with SLE and densitometry (p < 0.001). There was a significant relationship between CDVA and densitometry: for every 10 GSUs of increased densitometry in the 0-2 mm zone, CDVA worsened by approximately half a Snellen line (p < 0.001). Age and pre-operative Kmax were significant predictors of densitometry. For every 10 years of age, densitometry increased by 0.68 GSUs (95% CI [0.27 to 1.07], p < 0.001). For every 10 D of increased preoperative Kmax , densitometry increased by 0.69 GSUs (95% CI [0.41 to 0.98], p < 0.001). CONCLUSIONS: Subjective haze after aCXL estimated with SLE, is significantly associated with densitometry. Increased densitometry after aCXL is associated with a reduction in CDVA.

Congenital corneal staphyloma in 8q21.11 microdeletion syndrome.

BACKGROUND: Although 8q21.11 microdeletion syndrome (8q21.11 DS) has been reported in association with congenital corneal opacities, reports of the clinicopathological features and management are scarce. METHODS: We reviewed medical records including ophthalmic evaluations, imaging, operative reports, and pathology reports of two unrelated patients referred to the Ophthalmology Clinic of UPMC Children's Hospital of Pittsburgh with a cytogenetic diagnosis of 8q21.11 DS. RESULTS: Ophthalmological evaluation of both children revealed bilateral enlarged, staphylomatous, and cloudy corneas with neovascularization. These findings were consistent with the diagnosis of congenital corneal staphyloma (CCS). In one patient, anterior segment optical coherence tomography and high-frequency ultrasound revealed materials consistent with lens remnants embedded in the cornea; this was confirmed by histopathology. In the second patient, lens was found to be adherent to the cornea during surgery. One eye underwent enucleation for corneal perforation secondary to elevated intraocular pressure. In the other eyes, treatment consisted of penetrating keratoplasty combined with vitrectomy. Ahmed tube was subsequently placed to control intraocular pressure. CONCLUSION: 8q21.11 microdeletion syndrome can be associated with bilateral CCS, likely related to a combination of anterior segment developmental anomalies and elevated intraocular pressure. Tectonic penetrating keratoplasty is necessary to prevent corneal perforation, together with a strict control of the intraocular pressure.

Cumulative dissipated energy in eyes with and without corneal opacity.

Objective: To compare ultrasonic energy delivered into the eye [cumulative dissipated energy, (CDE)] and frequencies of required auxiliary surgical methods during phacoemulsification surgery in eyes with and without corneal opacity. Methods: The study was designed as a retrospective comparative observational study. The study group [Corneal Opacity Group, (COG)] was comprised of 31 eyes of 31 cataract patients with corneal opacity. Only nebular and macular corneal opacities (according to slit-lamp based classification of Agrawal) were included in the study. The control group (CG) was comprised of 40 eyes of 40 cataract patients without corneal opacity. The CDE values were obtained using the Centurion system (Alcon, Fort Worth, TX) and the patients were followed-up postoperatively for a period of one month. Results: The mean age of the subjects was 71.46 ± 8.86 years (52-89) in COG and 66.12 ± 5.96 years (55-80) in CG (p >0.05). In COG, the most common etiologic factors were trauma, keratitis, and degenerative diseases. The mean CDE value was 15.16 ± 8.71 (2.20-42.65) in COG and 10.04 ± 6.28 (3.77-31.80) in CG and it was found as significantly higher in COG (p=0.003). Some auxiliary surgical methods including posterior synechiolysis and anterior capsule staining were more commonly performed in COG (p=0.044 and p=0.040, respectively). No intraoperative or postoperative complication was observed. Conclusion: More ultrasonic energy is delivered into the eye and more auxiliary surgical methods are needed in cataract patients with corneal opacity who underwent phacoemulsification. Abbreviations: CDE = Cumulative dissipated energy, COG = Corneal Opacity Group, CG = Control group, IOL = Intraocular lens, LOCS = Lens Opacities Classification System, BCVA = best-corrected visual acuity, SRK/T = Sanders, Retzlaff, and Kraff theoretical, OVD = ophthalmic viscosurgical device, SPSS = Statistical Package for the Social Sciences.

A Case of Clinically Atypical Gelatinous Drop-like Corneal Dystrophy With Unilateral Recurrent Amyloid Depositions.

PURPOSE: The purpose of this article was to describe the successful diagnosis and management of clinically atypical, unilateral, gelatinous drop-like corneal dystrophy (GDLD) in a pediatric patient. METHODS: This study was a case report. RESULTS: A 7-year-old Japanese girl was referred to our clinic with right corneal opacity for over 3 years. Slitlamp examination revealed a white, protruding, paracentral corneal opacity with an irregular surface and tiny stromal lattice figures with subepithelial opacities. No trichiasis or epiblepharon was observed, and the patient's right corrected distance visual acuity (CDVA) was 18/20. The contralateral cornea was intact but demonstrated fluorescein uptake. After 8 months, the right CDVA worsened from 18/20 to 6/20, and corneal epithelial scraping was performed. Histopathological analysis revealed amyloid nodules in the subepithelial layer and in the anterior corneal stroma stained with Congo red, which reoccurred 2 months after the procedure, and corneal dystrophy was suspected. Isolation and sequencing of the genomic DNA revealed a homozygous p.Gln118Ter. mutation in TACSTD2 in the patient and heterozygous p.Gln118Ter. mutations in both parents. GDLD was diagnosed; bilateral use of therapeutic soft contact lenses was prescribed after the first corneal scraping. No additional surgical intervention was required for the right eye for 4.5 years. CDVA of the contralateral left eye has been successfully maintained at 30/20 over this period, without emergence of nodular lesions or corneal opacities. CONCLUSIONS: We encountered a patient with early, atypical GDLD, who was definitively diagnosed using genomic DNA sequencing. GDLD should be a part of the differential diagnosis in patients presenting with unilateral, recurrent amyloid deposition.

Opacidades corneales en niños / Corneal Opacities in Children

Si en el período temprano de la vida ocurre alguna condición que no permita una adecuada estimulación visual se produce la ambliopía por deprivación. Las afecciones corneales que se diagnostican en los niños pueden tener un origen congénito o adquirido, este último traumático o no. El conocimiento del diagnóstico de las afecciones que ocasiona opacidad corneal en niños es determinante para poder obtener todos los elementos necesarios que ayuden a identificar un diagnóstico lo más temprano y preciso posible y proveer una adecuada guía para escoger estrategias de tratamiento, por parte del equipo multidisciplinario involucrado. El objetivo fue abordar de manera actualizada las características en el diagnóstico y tratamiento de las opacidades corneales en edades pediátricas. Se realizó una búsqueda automatizada sobre el tema teniendo en cuenta las publicaciones de los últimos cinco años. Se utilizó la plataforma Infomed, específicamente la Biblioteca Virtual de Salud(AU)

If any medical condition that does not allow adequate visual stimulation manifests early in life, deprivation amblyopia follows. Corneal conditions diagnosed in children may have a congenital or acquired origin, the latter being traumatic or not. Knowledge of the diagnosis of conditions that cause corneal opacity in children is crucial to obtain all the necessary elements to help identify the earliest and most accurate diagnosis possible and to provide an adequate guide to choose treatment strategies by the multidisciplinary team involved. The objective was to address in an updated way the characteristics in the diagnosis and treatment of corneal opacities in pediatric ages. An automated search on the subject was carried out taking into account the publications of the last five years. The Infomed platform was used, specifically the Virtual Health Library(AU)

A novel homozygous frameshift mutation in the APOA1 gene associated with marked high-density lipoprotein deficiency.

The proband was a 53-year-old Japanese woman. Despite having no atherosclerotic vascular lesions on a physiological examination, markedly decreased levels of high-density lipoprotein (HDL) were always noted at her annual medical checkup. She also had corneal opacities but neither xanthoma nor tonsillar hypertrophy. A biochemical examination showed decreased levels of both apolipoprotein A-I (apoA-I) (<5 mg/dL) and lecithin-cholesterol acyltransferase (LCAT) activity. Her brother and son also had low concentrations of HDL-cholesterol, suggesting the presence of a genetic abnormality. Therefore, a sequence analysis of the genes for ABCA1, LCAT and apoA-I proteins was performed in the proband. The analysis of the APOA1 gene revealed a novel homozygous two-nucleotide deletion in exon 4 (c.614_615delTC), which causes a frameshift after residue 205 of the apoA-I protein (p.Leu205fs). Since no mutation has been found in the ABCA1 or LCAT gene, functional abnormalities of the carboxyl-terminal region of the apoA-I protein in lipid binding might have caused the low HDL-cholesterol levels and decreased LCAT activity, possibly associated with corneal opacities but not premature CAD, in the patient.

Endoilluminator-aided cataract surgery in eyes with corneal opacity - A modified surgical approach.

Background: Cataract and corneal blindness continue to be leading causes of reversible blindness in India. These can co-exist in a multitude of pathologies such as trauma, healed keratitis (old herpetic scar), chronic degenerative changes such as labrador keratopathy, bullous keratopathy, corneal dystrophies etc. Phacoemulsification in such eyes is rewarding to the patient in terms of minimal intervention, less risk of complications owing to reduced open sky time (as in case of combined keratoplasty), and better predictable visual outcomes. Approach to such eyes with poor visualisation is highly challenging. Purpose: We illustrate a modified surgical technique of chandelier illumination through pars plana for cataract surgery in eyes with corneal opacity of varying grades. Synopsis: Five patients with dense cataract and small pupils, associated with corneal opacity (leucomatous and macular grade) are described. Closed chamber phacoemulsification with intraocular lens with or without pupil expanders was performed assisted by 23 or 25 gauge pars plana chandelier illumination introduced in the vitreous cavity through a sclerotomy wound made prior to phacoemulsification in the inferotemporal quadrant. Highlights: Chandelier illumination aids in reducing the light scatter that occurs due to corneal opacity. Ease of visualisation of lens structures and of performing cataract surgery was noticed. One case was combined with penetrating keratoplasty with reduced open sky time. This assisted technique has advantages such as enhancing visualisation intraoperatively and allowing working in closed chamber. Its self-retaining nature aids bimanual manipulation. No complications were encountered. The video highlights the utility, advantages and practicality of chandelier retroillumination in patients with corneal opacities of varying degree undergoing phacoemulsification. Video Link: https://youtu.be/I3z6QG-_wD8.

Surgical approach in type II Peters anomaly - case report.

Objective: The aim of this report was to present a rare case of apparently unilateral Peters anomaly and describe the clinical characteristics, surgical approach, and visual prognosis. Methods: We presented the case of a 7-year-old female patient with posterior corneal defect due to kerato-lenticular adhesions along with anterior dislocation and opacification of the lens in the left eye and a history of post-traumatic evisceration of the right eye. Systemic associations included mental underdevelopment, left torticollis and scoliosis. No family history of acquired or inherited diseases were determined. We performed cataract extraction in the left eye and opted for aphakia. Results: Based on clinical findings, we considered unilateral Peters anomaly type II. Cataract surgery slightly improved the visual acuity from hand moving to 20/ 400 UCVA (uncorrected visual acuity) and 20/ 100 with +10.0 diopters at 1 month postoperative. No enlargement of the corneal opacity was observed. Conclusions: In this case, we were able to diagnose Peters anomaly only in one eye. The diagnosis required long follow-up with periodic measurement of intraocular pressure (IOP) to early detect glaucoma. The complexity and uniqueness of the case relied on the difficult approach made by the cloudy cornea and anterior lens dislocation. We applied a combination of techniques including adhesiolysis, cataract extraction and anterior vitrectomy. Further interventions such as secondary IOL (intraocular lens) implantation or PKP (penetrating keratoplasty) will be taken into consideration after six-month and one-year postoperative follow-up. Abbreviations: PA = Peters anomaly, DM = Descemet's membrane, IOL = intraocular lens, VA = visual acuity, OVDs = ophthalmic viscosurgical devices, IOP = intraocular pression, PKP = penetrating keratoplasty, BCVA = best corrected visual acuity, UCVA = uncorrected visual acuity.

[Optical rehabilitation and pediatric ophthalmological care following keratoplasty for childhood corneal opacities]. / Optische Rehabilitation und kinderophthalmologische Betreuung nach Keratoplastik bei kindlichen Hornhauttrübungen.

BACKGROUND: The younger the children are at the time of corneal transplantation, the worse the survival prognosis of the graft. PREOPERATIVE CONSIDERATIONS: Preoperative considerations are significant in terms of accurate parental education, ensuring adherence to treatment and choosing the appropriate surgical time frame (amblyopia versus graft failure, compliance of the patient). Parental education must include the reduced visual prognosis in young children, exceptions being later acquired corneal pathologies such as inflammatory corneal scars (herpes) and keratoconus. POSTOPERATIVE CARE: A distinction must be made between morphological care after transplantation and refractive correction as well as treatment of amblyopia. The younger the children, the less favorable the prognosis for the transplant and the more often multiple examinations with anesthesia are necessary in order to detect complications, such as infiltrates or suture loosening at an early stage. Especially unilateral congenital pathologies often do not lead to a sufficient improvement of amblyopia (refractory amblyopia, poor compliance). CONCLUSION: The prognosis after keratoplasty in childhood is already partly decided by the careful evaluation of indications (no surgery of a sclerocornea) and the detailed and realistic clarification for the parents (cooperation with long-term ocular and systemic treatment even if the child has poor compliance, frequent check-ups, reduced chances of amblyopia treatment). The younger the child is at the time of transplantation, the more frequent are graft failure and the development of complications. Later manifesting diseases in older children (herpetic corneal scars, keratoconus) have a better prognosis.

Clinical Dilemma of Corneal Opacity, Very Low High-density Lipoprotein, and Nephrotic Syndrome: Mystery Revealed.

Lecithin-cholesterol acyltransferase (LCAT) is a liver enzyme necessary for the formation of cholesteryl esters in plasma from free cholesterol. The rare autosomal recessive disease resulting from familial deficiency of this enzyme can lead to nephropathy with kidney involvement generally being the most common cause of death. In addition, the disease process can engender corneal opacity, very low high-density lipoprotein, normochromic anemia, and nephropathy. We present this case of a 35-year-old male who initially visited for a second opinion for renal failure and nephrotic range proteinuria. He underwent renal biopsy which displayed focal segmental glomerulosclerosis-type injury pattern and was started on futile high-dose steroid therapy. A second renal biopsy coincided with the development of corneal opacity leading to a confirmatory testing of LCAT deficiency through biochemistry panel.

Acute Calcific Band Keratopathy as an Adverse Effect of Recombinant Human Nerve Growth Factor (Cenegermin): A Multicenter Case Series.

PURPOSE: Cenegermin, (OXERVATE) a recently Food and Drug Administration-approved topical formulation of recombinant human nerve growth factor, has been used for the treatment of neurotrophic keratopathy (NK). Corneal deposits have been previously reported as a potential adverse effect; however, the clinical characteristics, visual significance, and treatment options have not been fully described. The purpose of this article is to better characterize corneal deposits occurring during treatment with cenegermin for neurotrophic keratopathy. METHODS: This was a retrospective, multicenter consecutive case series. RESULTS: We identified 5 patients from 3 institutions who developed a white opacity in varying layers of the cornea, consistent with calcium deposition, during treatment with cenegermin. In all cases, the opacity occurred rapidly over the course of a few weeks after initiation of treatment. Histopathologic examination of the cornea from one corneal patient demonstrated extensive calcification of the stroma extending to 90% depth. Before treatment, all patients had stage 2 or 3 NK (Mackie classification). The deposits were visually significant in all patients and did not resolve after cessation of cenegermin. There were no differences in age, sex, etiology of the NK, corneal transplant status, or concurrent medications between the patients who developed a deposit and 15 other patients with stage 2 or 3 NK who did not. One patient was successfully treated with superficial keratectomy with ethylenediaminetetraacetic acid chelation, one patient underwent penetrating keratoplasty, and one patient received a Boston keratoprosthesis. CONCLUSIONS: We report the rapid onset of a corneal opacity after initiation of treatment with cenegermin in patients with stage 2 or 3 NK, consistent with acute calcific band keratopathy. This visually significant adverse finding has not previously been described. We could not identify any risk factors for development. We recommend close monitoring of patients receiving cenegermin therapy because the opacity may be irreversible and may require keratoplasty for visual rehabilitation.

Late Onset Interface Calcium Deposition After Laser In Situ Keratomileusis.

PURPOSE: The purpose of this study was to report a novel clinical entity characterized by bilateral calcium deposits in the flap interface after uncomplicated laser in situ keratomileusis (LASIK). METHODS: Slit-lamp examination, anterior segment optical coherence tomography imaging, and histopathologic analysis of an interface opacity were performed to characterize and identify the origin of the interface opacities. RESULTS: Two unrelated healthy young men who underwent LASIK in both eyes at 20 (case 1) and 44 (case 2) years of age were diagnosed with bilateral, white anterior stromal opacities 5 years after LASIK surgery. Slit-lamp examination and anterior segment optical coherence tomography imaging demonstrated that the opacities were located at the level of the LASIK interface in both eyes of both cases, with most of the opacities located at the temporal edge of the flap in each eye of case 2. An opacity from case 2 demonstrated birefringence using polarization microscopy and staining with Alizarin red, indicative of calcium deposition. The serum calcium level was borderline elevated in case 1 and within normal limits in case 2. CONCLUSIONS: Intrastromal calcium deposition can occur after LASIK surgery, with the deposits resembling dystrophic deposits located in the LASIK flap interface in individuals with granular corneal dystrophy type 2. Because the etiology and management of calcific and dystrophic interface deposition after LASIK are distinct, it is important for clinicians to differentiate the 2 entities based on the examination, diagnostic imaging, and, if necessary, molecular genetic analysis.

Bilateral ocular deposit of chlorpromazine / Depósito ocular bilateral de clorpromazina

ABSTRACT Chlorpromazine is a medication widely used in psychiatry for the treatment of psychoses, especially schizophrenia. Since 1964, published articles have been correlating this medication with the appearance of ocular alterations. In this paper, we report the case of a 65-year-old patient with ocular effects due to long-term therapy with chlorpromazine. Biomicroscopy of both eyes presented diffuse granular brown deposits, most prominent at the deep stroma and corneal endothelium level. Also showed anterior subcapsular brown deposits with a stellate pattern in the lens. The total amount exceeds 2.000g (significant for the ocular alterations described) considering the patient's daily dosage of chlorpromazine of 300mg for ten years. After performing complete ophthalmic evaluation and discarding other causes for the ocular deposits, we diagnosed a secondary corneal deposit and cataract due to the use of chlorpromazine. This case reinforces the importance of periodic follow-up with an ophthalmologist for chlorpromazine users to trace ocular changes, heeding the exposure time and its dosage.

RESUMO A clorpromazina é uma medicação muito empregada na psiquiatria para tratamento de psicoses, especialmente em casos de esquizofrenia. Desde 1964 existem artigos publicados que correlacionam o uso dessa medicação com o aparecimento de alterações oculares. Neste trabalho, relatamos o caso de um paciente de 65 anos com efeitos oculares devido à terapia de longo prazo com clorpromazina. A biomicroscopia de ambos os olhos apresentou depósitos granulares difusos e de cor marrom, mais proeminente ao nível do estroma profundo e do endotélio da córnea, além de depósitos castanhos subcapsulares anteriores centrais em um padrão estrelado no cristalino. Considerando a dose diária de clorpromazina de 300mg por 10 anos usada pelo paciente, a quantidade total ultrapassa 2.000g (dose considerada significativa para as alterações oculares descritas). Após avaliação oftalmológica completa e descartado outras causas desses depósitos oculares, foram diagnosticados depósito corneano e catarata secundários ao uso de clorpromazina. O caso apresentado reforça a importância do acompanhamento oftalmolÓgico periÓdico de usuários de clorpromazina para o rastreio de alteraçÕes oculares, atentando-se ao tempo de exposição à droga e à posologia da mesma.

Simple and novel technique of using lampblack soot as a corneal tattoo for disfiguring corneal opacities.

The aim of this study was to report a series of corneal tattooing in three eyes of three patients with disfiguring corneal scar and no visual potential, which underwent the procedure using the lampblack prepared in the operating room (OR), and to describe the novel technique of lampblack preparation for the surgery. The depth of corneal opacity was carefully assessed and a superficial lamellar pocket was made by lamellar separation using corneal dissectors, following which the prepared lampblack soot using materials available in the OR was deposited in the pocket. At a mean follow-up of 6 months, all the eyes had a stable corneal surface with an acceptable cosmetic outcome. Corneal tattoo using lampblack gives a satisfactory cosmetic result with good patient satisfaction and improved quality of life in the eyes with disfiguring corneal scar.