Prediction of total corneal power in keratoconus using anterior surface data.

CLINICAL RELEVANCE: Keratoconus results in an increase in anterior and posterior curvatures and a reduction in corneal thickness. Anterior corneal ectasia is partially compensated by remodelling the corneal epithelium. Therefore, there is an alteration in the relationship between corneal surfaces and variation in corneal power. The variation in corneal power is one of the sources that induces errors in IOL power calculation. BACKGROUND: This study aimed to assess a method for predicting total corneal power in keratoconus using several anterior surface parameters at 3 mm and 4 mm. METHODS: Tomographic data obtained using Pentacam (Oculus, Germany) were analysed from 280 eyes of 140 patients with keratoconus using anterior and posterior keratometry, anterior Q-value at 8 mm, central corneal thickness, Kmax location and value, and true net power at 4 mm (TNP). Calculated total corneal power (TCPc) at 3 mm was obtained using the Gauss formula. Predicted total corneal power at 3 mm (TCPp3) and 4 mm (TCPp4) was obtained from univariate (TCPp3u and TCPp4u) and multivariate linear regression formulae (TCPp3m and TCPp4m). SimK, anterior Q-value, vertical location, and Kmax value were used in the multivariate formulae. Mean absolute error (MAE) and median absolute error (MedAE) were also calculated. Absolute frequencies within dioptric ranges of all formulas divided for keratoconus grading were evaluated. RESULTS: TCPc and TNP exhibited a good correlation (R2 = 0.58, p < 0.05) with a higher dispersion above 50 D of corneal power. Highly significant correlations were observed between TCPp3u and TCPc (R2 = 0.978, p < 0.05) and TCPp3m and TCPc (R2 = 0.989, p < 0.05). Lower but significant correlations were observed between TCPp4u and TNP (R2 = 0.692, p < 0.05) and between TCPp4m and TNP (R2 = 0.887, p < 0.05). The best results for TCP prediction at 3 and 4 mm were obtained with TCPp3m and TCPp4m as follows: MAE of TCPp3m was 0.24 ± 0.20 (SD) D with MedAE of 0.20 D, while MAE of TCPp4m was 0.96 ± 0.77 D with MedAE of 0.80 D. The 3 mm multivariate regression formula results in higher absolute frequencies of prediction errors in the total eyes within 0.5 D (93%) than the univariate formula (81%). At 4mm, the multivariate regression formula has a lower percentage within 0.5 D (32%) than the univariate formula (41%), but the percentage of the multivariate formula is higher within 1 D (63%) than the univariate formula (56%). CONCLUSION: All formulas show a decrease in accuracy with increasing grades of keratoconus. Multivariate linear regression formulae using only anterior surface data can predict TCP with good approximation in eyes with keratoconus in cases where posterior surface parameters are unavailable. The vertical location of Kmax and the anterior asphericity could play a relevant role in the prediction of total corneal power in keratoconus.

Clinical Results of Accelerated Iontophoresis-Assisted Epithelium-on Corneal Cross-linking for Progressive Keratoconus in Children.

PURPOSE: To evaluate the clinical characteristics of pediatric patients with progression of keratoconus after accelerated iontophoresis-assisted epithelium-on corneal cross-linking (I-ON CXL) and to assess the efficacy and safety of re-treatment using accelerated epithelium-off CXL (epi-OFF CXL). METHODS: Sixteen eyes of 16 patients (mean age: 14.6 ± 2.5 years) with keratoconus underwent I-ON CXL. The main outcome measures were uncorrected distance visual acuity, corrected distance visual acuity, maximum keratometry index (Kmax), minimum corneal thickness, elevation front and elevation back measured at the thinnest point, total higher order aberrations root main square (HOA RMS), coma RMS, and spherical aberration. An increment of Kmax greater than 1.00 diopter (D) and a decrease of greater than 20 µm in pachymetry were considered to determine the progression of keratoconus. Patients with progression of keratoconus after I-ON CXL were re-treated using an epi-OFF CXL protocol. RESULTS: Two years after I-ON CXL, 12 patients showed progression of keratoconus, whereas 4 patients were stable. There was significant worsening of Kmax (P = .04) and steepest keratometric reading (P = .01). Furthermore, a significant correlation was documented between progression of keratoconus and age (P = .02). These patients were re-treated using an epi-OFF protocol and after 2 years all patients were stable, and a statistically significant reduction of the mean Kmax (P = .007), HOA RMS (P = .05), and coma RMS (P = 05) was observed. CONCLUSIONS: I-ON CXL was ineffective in the treatment of pediatric keratoconus in younger children, whereas it had an efficacy of 2 years in older children. Re-treatment using epi-OFF CXL proved effective to halt progression of keratoconus after I-ON CXL failure. [J Pediatr Ophthalmol Strabismus. 2024;61(1):44-50.].

One-Year Results of Photorefractive Keratectomy for Myopia and Compound Myopic Astigmatism with 210 nm Wavelength All Solid-State Laser for Refractive Surgery.

BACKGROUND: To examine the 12-month clinical and refractive outcomes of PRK performed with a UV all-solid-state laser. METHODS: The study included healthy patients with myopia and/or compound myopic astigmatism enrolled for refractive surgery and treated with PRK using a 210 nm wavelength, 2 kHz repetition rate, UV all-solid-state laser (LaserSoft, Katana Technologies GmbH, Kleinmachnow, Germany). All subjects were examined at baseline and after 1, 3, 6, and 12 months after the treatment with a slit lamp, refraction, visual acuity assessment (logMAR chart), tonometry, ophthalmoscopy, and corneal tomography with a Scheimpflug camera. The outcome measures considered were uncorrected (UDVA) and corrected (CDVA) distance visual acuities, refraction, central corneal thickness, and transparency. The efficacy, safety, predictability, and stability were determined. RESULTS: The study included 34 eyes of 19 patients. The mean UDVA changed from 1.20 ± 0.43 to -0.05 ± 0.10 logMAR at 12 months, and the mean CDVA changed from -0.03 ± 0.06 to -0.06 ± 0.09 logMAR, respectively. The mean spherical equivalent (SE) changed from -4.90 ± 2.12 D to -0.01 ± 0.40 D and was within ±0.50 D of the intended correction in 91% of eyes and within ±1.00 D in 97% of eyes at 12 months. No eyes lost lines of visual acuity, and 64% of eyes gained one or more lines. CONCLUSIONS: PRK with the 210 nm wavelength, 2 kHz repetition rate, all-solid-state laser LaserSoft system proved to have good visual, refractive, and clinical outcomes after the follow-up at 12 months. The emerging gas-free, solid-state technology might be considered a valid alternative for the gas operating lasers for corneal refractive surgery.

Clinical Evaluation of the Efficacy of Femtosecond Laser-Assisted Anterior Lamellar Keratoplasty.

BACKGROUND: To evaluate the clinical outcome, efficacy, and safety of femtosecond laser-assisted anterior lamellar keratoplasty. MATERIAL AND METHODS: In this prospective study, 21 males and 10 females aged from 15 to 62 years (mean 38.5) with different pathologies of the anterior corneal layers were enrolled for anterior lamellar keratoplasty using femtosecond laser VisuMax (Carl Zeiss, Germany). All patients were examined for uncorrected (UCVA) and best-corrected (BCVA) distance and near visual acuity, astigmatism, endothelial cell density, corneal thickness, and intraocular pressure. These examinations were performed before transplantation, at hospital discharge, and after 3 and 12 months. The mean follow-up time was 65.36 ± 28.54 months. RESULTS: A statistically significant improvement of both UCVA and BCVA for distance and near vision was registered. BCVA improved from 0.11 preoperatively to 0.168 (p = 0.03), 0.267 (p < 0.01), and 0.472 (p < 0.01) on the hospital discharge day, three months, and 12 months respectively. There were no statistically significant differences in astigmatism, intraocular pressure, endothelial cell density, and corneal pachymetry as compared to preoperative and postoperative values. Six patients (19%) had a graft failure with a rate of 33% at 26 months. CONCLUSIONS: Femtosecond laser-assisted anterior lamellar keratoplasty is a safe and effective surgical method, providing satisfactory graft survival rates.

Corneal Sub-Basal Nerve Plexus in Non-Diabetic Small Fiber Polyneuropathies and the Diagnostic Role of In Vivo Corneal Confocal Microscopy.

In vivo corneal confocal microscopy (IVCM) allows the immediate analysis of the corneal nerve quantity and morphology. This method became, an indispensable tool for the tropism examination, as it evaluates the small fiber plexus in the cornea. The IVCM provides us with direct information on the health of the sub-basal nerve plexus and indirectly on the peripheral nerve status. It is an important tool used to investigate peripheral polyneuropathies. Small-fiber neuropathy (SFN) is a group of neurological disorders characterized by neuropathic pain symptoms and autonomic complaints due to the selective involvement of thinly myelinated Aδ-fibers and unmyelinated C-fibers. Accurate diagnosis of SFN is important as it provides a basis for etiological work-up and treatment decisions. The diagnosis of SFN is sometimes challenging as the clinical picture can be difficult to interpret and standard electromyography is normal. In cases of suspected SFN, measurement of intraepidermal nerve fiber density through a skin biopsy and/or analysis of quantitative sensory testing can enable diagnosis. The purpose of the present review is to summarize the current knowledge about corneal nerves in different SFN. Specifically, we explore the correlation between nerve density and morphology and type of SFN, disease duration, and follow-up. We will discuss the relationship between cataracts and refractive surgery and iatrogenic dry eye disease. Furthermore, these new paradigms in SFN present an opportunity for neurologists and clinical specialists in the diagnosis and monitoring the peripheral small fiber polyneuropathies.

Effects of the Topical Use of the Natural Antioxidant Alpha-Lipoic Acid on the Ocular Surface of Diabetic Patients with Dry Eye Symptoms.

PURPOSE: The purpose of this study is to investigate the effects of the treatment with eye-drops based on a combination of antioxidant and mucomimetic molecules, namely 0.1% alpha-lipoic acid (ALA) and 0.3% hydroxy-propyl-methylcellulose (HPMC) on the ocular surface of diabetic patients with dry eye symptoms. METHODS: Seventy patients, 42 M and 28 F, aged from 50 to79 years (mean 62.1 ± 10.5), affected by type II diabetes mellitus, were enrolled and divided in two groups treated for 2 months as follows: Group 1 (35 patients), received topical ALA/HPMC three times a day, Group 2 (35 patients) received topical HPMC (0.3%) alone, three times a day. The main outcome measures were: Ocular Surface Disease Index (OSDI), tear film break-up time (TBUT), corneal fluorescein staining, Schirmer I test, corneal sensitivity. An examination of tear film morphology with confocal microscopy was carried out in a subset of patients of each group at baseline and after two months. Statistical analysis was performed with t-test for the parametric data and Mann-Whitney U-test or chi-squared test for the nonparametric data. RESULTS: Both treatments resulted in significant improvements of BUT, OSDI and tear film morphology, although the improvements observed in group 1 showed a higher trend than what observed for group 2. Moreover, only in group 1 a significant improvement was visible for corneal staining, and no significant improvements were observed in any group for Schirmer I and sensitivity. CONCLUSIONS: These results confirmed the efficacy of HPMC in the treatment of diabetic dry eye and indicated that the addition of a strong self-regenerating antioxidant like ALA may give a distinctive advantage for the healing of corneal defects (as evidenced by corneal staining), beside improving HPMC efficacy on three other parameters (BUT, OSDI score, tear morphology). Therefore, the addition of a strong antioxidant like ALA can be helpful in preventing or treating ocular surface defects in diabetic patients, in which the oxidative damage is predominant.

Clinical and instrumental assessment of the corneal healing in moderate and severe neurotrophic keratopathy treated with rh-NGF (Cenegermin).

PURPOSE: To evaluate corneal healing in patients with moderate and severe neurotrophic keratitis (NK) treated with topical rh-NFG (Cenegermin). METHODS: Twenty-one patients (12F and 9M) aged from 21 to 93 years (62.5 ± 19.4) with moderate and severe NK were enrolled in the study. The patients were divided into 2 groups accordingly to the severity of the disease. The underlying causes of NK were determined. The VAS questionnaire was dispensed. The ocular examination comprised slit lamp evaluation, ocular surface assessment with Keratograph 5M (Oculus, Germany), corneal sensitivity with Cochet-Bonnet esthesiometer (Lunneaux, France) and corneal thickness measurement with AC-OCT (DRI, Triton, Topcon, Japan). The drops of Cenegermin 0.002% were administrated 6 times daily for 8 weeks. All participants were evaluated at baseline, after 4 and 8 weeks of the treatment. The area of corneal defect with maximum diameter less than 0.5 mm was considered as healed. The main outcome measures were corneal healing, corneal sensitivity recovery and corneal thickness in the ulcer group. RESULTS: The herpetic keratitis was the most common cause of NK. Thirteen eyes were affected by severe grade of NK with corneal ulcer and 8 eyes presented a moderate grade. After 8 weeks a complete healing of the corneal defects was registered both in moderate and severe NK. Significant increase of the corneal sensitivity and thickness were registered. CONCLUSIONS: The rh-NGF (Cenegermin) resulted effective in the treatment of the severe and moderate NK with significant recovery of the corneal sensitivity and healing of the corneal defects in both groups.

The Role of Hi-Tech Devices in Assessment of Corneal Healing in Patients with Neurotrophic Keratopathy.

To prove the role of high-tech investigation in monitoring corneal morphological changes in patients with neurotrophic keratopathy (NK) using Keratograph 5M (K5M) and anterior segment OCT (AS-OCT), corneal healing was monitored with Keratograph 5M (Oculus, Wetzlar, Germany) and AS-OCT (DRI, Triton, Topcon, Tokyo, Japan) in 13 patients (8F and 5M), aged from 24 to 93 years (67.8 ± 19) with severe NK, who were treated with Cenegermin 0.002% (20 µg/mL) (Oxervate®, Dompè, Farmaceutici Spa, Milan, Italy). The surface defects were evaluated on Keratograph 5M with ImageJ software and the corneal thickness variations were measured using DRI-Triton OCT software. Instrumental procedures were performed at baseline, and after 4 and 8 weeks of the treatment, respectively. The main outcome measures were reduction of the ulcers' area and corneal thickness recovery. The mean area of the corneal ulcers was reduced between baseline and 4 weeks examination in all patients, and at 8 weeks all ulcers were completely healed. An increase of the corneal thickness was evidenced between the baseline visit and after the 4- and 8-week follow-up, respectively. Additionally, only in collaborating subjects the In Vivo Confocal Microscopy (IVCM) was performed with HRT Rostock Cornea Module (Heidelberg Eng GmbH) to study the corneal nerves fibres. High-tech diagnostics with K5M, AS-OCT and IVCM proved useful in the assessment of corneal morphology and the healing process in patients with NK and could be extended to assess other corneal pathologies.

Is keratoconus associated to thyroid diseases? Assessment of the corneal parameters in patients with congenital hypothyroidism.

PURPOSE: To investigate the association between keratoconus and congenital hypothyroidism (CH). PATIENTS AND METHODS: Patients were enrolled in this study and divided into two groups. The first group comprised 31 subjects (11M:20F) with the mean age of 15.2 ± 3.9 years. affected by CH, and the control group was composed by 19 healthy individuals (8M:11F) aged 14.3 ± 4.6 years. All patients underwent complete ophthalmologic examination with visual acuity assessment, refraction, slit lamp examination, and retinoscopy. Corneal parameters were measured using Scheimpflug camera (Pentacam® Oculus, Germany). The main outcome measures considered for evaluation were: average corneal curvature (K), central corneal thickness (CCT), anterior elevation and posterior elevation at the thinnest point, corneal volume (CV), anterior chamber depth (ACD), and anterior chamber volume (ACV). Additionally, data from Belin/Ambrosio Enhanced Ectasia Display (BAD) and the high order aberrations were evaluated. Kolmogorov-Smirnov test was used to verify the Gaussian distribution, the comparison between the controls and cases group was performed by Mann-Whitney nonparametric test. A p value less than 0.05 was considered to be statistically significant. The odds ratio was performed in order to quantify the relationship between the congenital hypothyroidism and abnormal values displayed on front BAD. RESULTS: The significant difference in the refractive status between both groups was observed. As to examined corneal and anterior chamber parameters no statistical differences were detected. CONCLUSIONS: Congenital hypothyroidism diagnosed and treated since the early postnatal life doesn't induce abnormalities of corneal parameters suggestive for keratoconus.

Combined Phialemonium curvatum and Acanthamoeba Keratitis: The Importance of Early Diagnosis and Specific Therapy.

PURPOSE: To report the clinical and confocal findings of a unique case of combined Phialemonium curvatum and Acanthamoeba keratitis and to highlight the role of the prompt diagnosis and specific medical treatment in preserving visual function. METHODS: A case report and literature review. RESULTS: A 54-year-old woman presented with a 3-day history of visual impairment, photophobia, and ocular pain in her right eye. Her best corrected visual acuity was 0.4 Logarithm of the Minimum Angle of Resolution scale, and the slit-lamp examination showed whitish corneal stromal infiltrate with satellite lesions. In vivo confocal microscopy evidenced Acanthamoeba cysts and fungal hyphae that resulted P. curvatum in the culture examination. The intensive medical treatment was started with topical 0.02% polyhexamethylene biguanide, voriconazole 1%, and moxifloxacin hydrochloride 0.5%. Progressive improvement of clinical and confocal pictures was registered with a complete recovery of visual function after 1 month. CONCLUSIONS: This is the first case report of combined P. curvatum and Acanthamoeba keratitis. The fast diagnosis with in vivo confocal microscopy allowed early and intensive specific treatment with recovery of corneal infection.

Oral Aminoacids Supplementation Improves Corneal Reinnervation After Photorefractive Keratectomy: A Confocal-Based Investigation.

Aim of this retrospective study was to estimate the effect of oral supplementation with amino acids (AA) on corneal nerves regrowth after excimer laser refractive surgery with photorefractive keratectomy (PRK). Based on the pre and post-surgical treatment received, 40 patients with 12 months of follow-up were distributed in two groups: 20 patients had received oral AA supplementation 7 days before and 30 days after PRK, and 20 patients without AA supplementation, as untreated reference control. All patients followed the same standard post-operative topical therapy consisting of an association of antibiotic and steroid plus sodium hyaluronate during the first week, then steroid alone progressively decreasing during 30 days and sodium hyaluronate for the following 3 months. In vivo corneal confocal microscopy was used to evaluate the presence of sub-basal corneal nerve fibers during 12 months after PRK. Results have shown that sub-basal nerves regenerated significantly faster (p <0.05), and nerve fibers density was significantly higher (p <0.05) with a more regular pattern in the eyes of AA treated patients with respect to the untreated control group. Therefore, our data indicate that oral supplementation with AA improved significantly corneal nerve restoration after PRK and could thus be considered as an additional treatment during corneal surgical procedures.

Severe Corneal Morphological Alterations after Excimer Laser Surface Ablation for a High Astigmatism.

We report long-term alterations of anterior corneal stroma after excimer laser surface ablation for a high astigmatism. The patient claimed progressive visual loss in his right eye (RE) during the last 3 years after bilateral laser-assisted subepithelial keratectomy (LASEK) surgery. His examination comprised visual acuity (UDVA and CDVA), slit-lamp examination, corneal topography and tomography, AS-OCT, and confocal microscopy. The UDVA was 0.1 in his RE and 1.0 in the left eye. The CDVA in the RE was 0.8. The slit-lamp examination showed a stromal lesion in the inferior paracentral corneal zone, with multiple vertical tissue bridges and severe thinning. Corneal topography and tomography showed central flattening with inferior steepening and severe alteration in elevation maps. AS-OCT showed void areas in the anterior stroma with thinning of the underlying tissue, and confocal images were not specific. In this case, progressive corneal steepening and thinning that manifest topographically as inferior ectasia occurred in correspondence to the singular stromal alterations after LASEK.

Impact of corneal parameters, refractive error and age on density and morphology of the subbasal nerve plexus fibers in healthy adults.

The purpose of this study was to analyze corneal sub-basal nerve plexus (SBNP) density and morphology and their relationships with corneal parameters and refractive status. In this single center study, in vivo confocal microscopy (IVCM) was performed in 76 eyes of 38 healthy subjects aged 19-87 (mean age 34.987 ± 1.148). Nerve fiber analysis was performed using Confoscan 4 microscope with semi-automated software (Nidek Technologies, Italy) The nerve fiber length (NFL) µm/mm2, nerve fiber density (NFD) no./mm2, tortuosity coefficient (TC), and nerve beadings density (NBD) no./mm were considered. Relationship between SBNP parameters and corneal curvature, thickness, diameter, and refraction were analyzed. Additionally, the association with gender, laterality and age were determined. NFL was inversely correlated with age (r = - 0.528, p < 0.001), myopic refractive error (spherical value) (r = - 0.423, p < 0.001), and cylindrical power (r = - 0.340, p = 0.003). NFD was inversely correlated with age (r = - 0.420, p < 0.001) and myopic refractive error (r = - 0.341, p = 0.003). NBD showed a low inverse correlation with cylindrical power (r = - 0.287, p = 0.012) and a slight positive correlation with K (r = 0.230, p = 0.047). TC showed a significant negative correlation between age (r = - 0.500, p < 0.001) and myopic refractive error (r = - 0.351, p = 0.002). Additionally, there were strong positive correlations between NFL and NFD (r = 0.523, p < 0.001), NFL and TI (r = 0.603, p < 0.001), and NFD and TC (r = 0.758, p < 0.001). Multiple regression analysis revealed age to be the most significant factor affecting SBNP density (B = - 0.467, p = 0.013) and length (B = - 61.446, p < 0.001); myopic refractive error reduced both SBNP density (B = - 2.119, p = 0.011) and length (B = - 158.433, p = 0.016), while gender and laterality had no significant effects (p > 0.005). SBNP fiber length decreases with age, myopic refractive error and cylindrical power. SBNP fiber density reduces with age and myopic refractive error. Corneal nerve parameters are not influenced by gender or laterality.

Corneal nerves in diabetes-The role of the in vivo corneal confocal microscopy of the subbasal nerve plexus in the assessment of peripheral small fiber neuropathy.

The cornea's intense innervation is responsible for corneal trophism and ocular surface hemostasis maintenance. Corneal diabetic neuropathy affects subbasal nerve plexus, with progressive alteration of nerves' morphology and density. The quantitative analysis of nerve fibers can be performed with in vivo corneal confocal microscopy considering the main parameters such as corneal nerve fibers length, corneal nerve fibers density, corneal nerve branching density, tortuosity coefficient, and beadings frequency. As the nerve examination permits the detection of early changes occurring in diabetes, the invivo corneal confocal microscopy becomes, over time, an important tool for diabetic polyneuropathy assessment and follow-up. In this review, we summarize the actual evidence about corneal nerve changes in diabetes and the relationship between the grade of alterations and the duration and severity of the disease. We aim at understanding how diabetes impacts corneal nerves and how it correlates with sensorimotor peripheral polyneuropathy and retinal complications. We also attempt to analyze the safety of the most common surgical procedures such as cataract and refractive surgery in diabetic patients and to highlight the specific risk factors. We believe that information about the corneal nerve fibers' condition obtained from the in vivo subbasal nerve plexus investigation may be crucial in monitoring peripheral small fiber polyneuropathy and that it will help with decision-making in ophthalmic surgery in diabetic patients.

Comparative Confocal and Histopathological Study of Corneal Changes in Multiple Myeloma.

PURPOSE: Corneal opacities rarely occur in multiple myeloma (MM). Our study correlates the findings of in vivo confocal microscopy (IVCM), a useful diagnostic tool, with histopathological features of corneal opacities appearing in a patient with MM. METHODS: Case report. RESULTS: A 53-year-old man developed corneal opacities in both eyes, more pronounced in the left eye. After IVCM examination, he underwent penetrating keratoplasty in the left eye, and the button was processed for light and electron microscopy and immunohistochemistry. The diagnosis of MM was made, as confirmed by the elevation of IgGk light chains. IVCM demonstrated hyperreflective areas at the epithelial level, hyperreflective keratocytes of dendritic and lamellar morphology in whole stroma, and hyperreflective endothelial cells. Histopathological examination disclosed many vacuoles in the epithelial cell cytoplasm and a homogenous granular material in the Bowman layer. In stroma, keratocytes of different shape and size, with vesicles laden with an abnormal material, were evident. In Descemet membrane, the posterior nonbanded zone had a honeycomb appearance because of the presence of many roundish spaces among wide-spaced collagen fibers. Endothelial cells demonstrated vesicles filled with a material of uneven electron density. Immunohistochemical analysis showed strong positivity for IgGk light chains in keratocytes and among stromal lamellae. CONCLUSIONS: This is the first study describing a correspondence between IVCM features and histopathological alterations observed in corneal opacities in MM. The results of this study improve the current understanding of the pictures obtained by IVCM studies.

Phenotype and genotype analysis in patients with macular corneal dystrophy.

AIM: The aim of this study was to analyse corneal morphological organisation and identify mutations in the carbohydrate sulfotransferase 6 gene (CHST6) in patients with macular corneal dystrophy originating in a Polish population. METHODS: Macular corneal dystrophy was diagnosed in 24 patients based on the slit-lamp exam, confocal microscopy, 1310 nm time domain and 840 nm spectral domain optical coherence tomography. 10 corneal buttons obtained from penetrating keratoplasty were processed for light microscopy. Genetic analysis of the CHST6 gene was performed, followed by a study of the sequencing results. RESULTS: Highly reflective, diffuse corneal deposits and a general increase in reflectivity were revealed with optical coherence tomography and confocal microscopy. The deposits extended from the Bowman layer to the Descemet membrane and correlated with the Alcian blue-positive granular-filamentous material into and around the stromal keratocytes confirmed by structural analysis of the corneal buttons. The genetic analysis of the blood samples identified the following mutations and single nucleotide polymorphisms: novel P64L (heterozygous), Y110C (homozygous), R162G and L200R, and M1L (heterozygous and homozygous). CONCLUSIONS: Genetic mutation heterogeneity was revealed. No phenotype heterogeneity was revealed among patients with in vivo corneal morphology assessment or histological analysis.

Phenotype-genotype correlation in patients with Schnyder corneal dystrophy.

PURPOSE: The aim of this study was to analyze the corneal morphology features and define mutations in the UbiA prenyltransferase domain-containing 1 (UBIAD1) gene in patients with Schnyder corneal dystrophy from a Polish population. METHODS: Five affected and 15 unaffected members originating from 3 families with Schnyder corneal dystrophy were included in the study. Phenotype analysis consisted of visual acuity, slit-lamp biomicroscopy with photography, time domain optical coherence tomography, spectral domain optical coherence tomography, and confocal microscopy. Three patients underwent a penetrating keratoplasty. Corneal buttons obtained from the penetrating keratoplasty were processed for light microscopy. RESULTS: A novel mutation I245N of the UBIAD1 gene was revealed in 1 proband and associated with the phenotype without central corneal opacities. The analysis of the other patients showed the N102S mutation. In vivo corneal morphology analysis using optical coherence tomography and confocal microscopy confirmed the presence of multiple crystalline corneal deposits in all affected corneas. The histological examination revealed multiple empty widenings of the corneal lamellae that could represent lipids removed from the specimen. CONCLUSIONS: N102S may also be a mutation hotspot in the Polish population, as in other previously reported populations. Corneal crystals formed a characteristic pattern on optical coherence tomography scans.

Macular corneal dystrophy: in vivo confocal and structural data.

OBJECTIVE: To demonstrate the corneal morphologic aspects obtained with in vivo confocal microscopy (CM) and light and electron microscopy of specimens obtained from the same patients with macular corneal dystrophy (MCD). DESIGN: Case series. PARTICIPANTS: Five consecutive patients affected by MCD undergoing penetrating keratoplasty (PK) in 1 eye. METHODS: The patients were examined with the slit-lamp, optical pachymetry, and CM before undergoing PK. The corneal buttons were processed for light, transmission, and scanning electron microscopy. MAIN OUTCOME MEASURES: Corneal in vivo CM, corneal light, and electron microscopy. RESULTS: Confocal microscopy showed areas of altered reflectivity in basal epithelial cells, which appeared hyperreflective or completely white. In the anterior stroma, rectilinear hyperreflective areas were shown. The stroma was characterized by a granular appearance of both keratocytes and extracellular matrix. Dark striae of different length and orientation were present in the middle and posterior stroma. The corneal endothelium showed polymegethism and cells containing bright granules in their cytoplasm. The histopathologic study demonstrated areas of thickened Bowman's layer covered by an epithelium reduced in height. The Bowman's layer thickenings were due to the accumulation of free or vesiculated material of different electron density. The keratocytes showed intracytoplasmatic vesicles, whereas the extracellular matrix presented a large quantity of intercellular electron-lucent material and parallel lamellae with an undulated course. Occasional macrophages, filled with vesicles of granular-filamentous material and evident podosomes, were observed. Descemet's membrane was formed by a normal anterior banded zone and a posterior nonbanded zone of honeycombed aspect. The endothelial cells showed a large number of intracytoplasmic vesicles. CONCLUSIONS: The structural changes observed with the histopathologic methods give an account and provide an explanation for the pathologic changes demonstrated by CM in the course of MCD. This may contribute to the understanding of in vivo imaging, allowing a better, noninvasive study of the disease evolution.