Corneal Epithelial Wavefront Error as a Novel Diagnostic Marker for Epithelial Basement Membrane Dystrophy.

Synopsis: Corneal epithelial wavefront error and epithelial thickness variance qualify as highly sensitive and specific biomarkers for epithelial basement membrane dystrophy (EBMD). The biomarkers show a normalization after treatment of EBMD with phototherapeutic keratectomy. Purpose: To gauge the diagnostic value of epithelial basement membrane dystrophy (EBMD), a novel spectral-domain optical coherence tomography (SD-OCT)-based imaging modality for simultaneous morphological (thickness profile) and refractive (optical wavefront) assessment of the corneal epithelial layer in one of the most common but often underdiagnosed corneal dystrophies. Methods: In this prospective observational study, a total of 32 eyes of 32 patients diagnosed with EBMD and 32 eyes of 32 healthy control subjects were examined with high-resolution anterior segment SD-OCT (MS-39; CSO, Florence, Italy). Various epithelial thickness and epithelial wavefront-derived terms were compared between groups and receiver operating characteristic (ROC) curves were computed to analyze the diagnostic capacity of the respective parameters. A total of 17 of 32 EBMD patients underwent treatment with phototherapeutic keratectomy (PTK) and were followed up for 3 months. Results: Epithelial thickness variance (60.4 ± 56.7 µm versus 7.6 ± 6.1 µm) and interquartile range (11.0 ± 6.9 versus 3.3 ± 1.9 µm) were markedly elevated in EBMD patients as compared with healthy controls (both with p < 0.001). Epithelial wavefront analysis showed a highly statistically significant excess in all examined aberration terms in EBMD patients (all with p < 0.001). Significantly greater areas under the curve (AUCs) were yielded by the epithelial wavefront-derived parameters (e.g., total epithelial wavefront error: AUC = 0.966; 95% confidence interval (CI) 0.932-1) than by the epithelial thickness-derived parameters (e.g., variance: AUC = 0.919; 95% CI 0.848-0.990). Conclusions: Corneal epithelial wavefront aberrometry proved valuable as an objective biomarker for EBMD, with high sensitivity and specificity. PTK resulted in a reduction of morphological and refractive epithelial irregularities in EBMD.

Hepatocyte Growth Factor Modulates Corneal Endothelial Wound Healing In Vitro.

In this study, we assessed the impact of hepatocyte growth factor (HGF) on corneal endothelial cells (CECs), finding that HGF concentrations of 100-250 ng/mL significantly increased CEC proliferation by 30%, migration by 32% and improved survival under oxidative stress by 28% compared to untreated controls (p < 0.05). The primary objective was to identify non-fibrotic pharmacological strategies to enhance corneal endothelial regeneration, addressing a critical need in conditions like Fuchs' endothelial dystrophy (FED), where donor tissue is scarce. To confirm the endothelial nature of the cultured CECs, Na+/K+-ATPase immunohistochemistry was performed. Proliferation rates were determined through BrdU incorporation assays, while cell migration was assessed via scratch assays. Cell viability was evaluated under normal and oxidative stress conditions using WST-1 assays. To ensure that HGF treatment did not trigger epithelial-mesenchymal transition, which could lead to undesirable fibrotic changes, α-SMA staining was conducted. These comprehensive methodologies provided robust data on the effects of HGF, confirming its potential as a therapeutic agent for corneal endothelial repair without inducing harmful EMT, as indicated by the absence of α-SMA expression. These findings suggest that HGF holds therapeutic promise for enhancing corneal endothelial repair, warranting further investigation in in vivo models to confirm its clinical applicability.

Epithelial Remodeling and Epithelial Wavefront Aberrometry after Spherical vs. Cylindrical Myopic Small Incision Lenticule Extraction (SMILE).

Background/Objectives: To compare the epithelial thickness changes and the changes in epithelial wavefront aberrometry following spherical versus astigmatic myopic small incision lenticule extraction (SMILE). Methods: Eighty-six eyes of 86 patients who underwent SMILE were included in this retrospective study. A total of 43 eyes underwent myopic spherical correction (spherical group) and 43 eyes underwent myopic cylindrical correction (cylindrical group). The groups were matched according to the spherical equivalent of surgically corrected refraction. Subjective manifest refraction as well as high-resolution anterior segment optical coherence tomography (MS-39; CSO; Florence, Italy) were obtained preoperatively as well as 3 months postoperatively. The latter was utilized for computing epithelial wavefront aberrometry in addition to epithelial thickness mapping. Results: Epithelial thickness increased significantly in both groups after SMILE (p < 0.01). In the cylindrical group, epithelial thickening was more pronounced on the flat meridian compared to the steep meridian (p = 0.04). In both groups, epithelial wavefront aberrometry showed a significant postoperative increase in the epithelium's spherical refractive power, causing a myopization of -0.24 ± 0.42 diopters (D) in the spherical group (p < 0.01) and -0.41 ± 0.52 D in the cylindrical group (p < 0.0001). While no significant changes in epithelial cylindrical refractive power were observed in the spherical group, a significant increase was noted in the cylindrical group from -0.21 ± 0.24 D to -0.37 ± 0.31 D (p = 0.01). In both groups, epithelial higher-order aberrations increased significantly (p < 0.001). Conclusions: Postoperative epithelial remodeling after SMILE alters lower-order (sphere and cylinder) and higher-order aberrations of the corneal epithelial wavefront and might contribute to refractive undercorrection, especially in astigmatic corrections. Epithelial wavefront aberrometry can be used to quantify the refractive effect of epithelial remodeling processes after keratorefractive surgery.

Enhancing ectasia screening using advanced AS-OCT: a case series of challenging refractive candidates.

Purpose: Ectasia screening in candidates for laser refractive surgery is mandatory during preoperative evaluation. Despite the availability of modern imaging techniques, refractive surgeons often face borderline decisions when patients present with suspicious tomographic findings. This case series presents refractive candidates with suspicious tomographic findings and demonstrates how to interpret them using Scheimpflug imaging and additional anterior segment optical coherence tomography (AS-OCT). Setting: Department of Ophthalmology, University Hospital, LMU Munich. Case series: This case series examines six potential candidates for refractive surgery with a mean age of 29.2 ± 3.9 years, whose corneal assessments using Scheimpflug imaging raised suspicion for ectasia. Each candidate was additionally examined with AS-OCT and reevaluated. The mean manifest subjective spherical equivalent was -3.67 ± 1.8 diopters. The total corneal thickness measured 537 µm ± 30 µm at its thinnest point. None of the candidates had any reported underlying corneal or ophthalmic diseases, and slit lamp examinations revealed no abnormal morphological findings. Conclusions: Both Scheimpflug imaging and AS-OCT are appropriate tools for screening refractive candidates for ectasia. While topographic and elevation analyses yielded comparable results regarding corneal structure, the epithelial mapping provided by AS-OCT played a critical role in decision-making for cases with borderline tomographic findings. Establishing a global consensus on the use of epithelial mapping in ectasia screening is necessary.

[Keratoplasty - an Overview of the Methods and their Perioperative Management]. / Keratoplastik ­ Übersicht der Verfahren mit ihrem perioperativen Management.

Corneal transplantation can be divided into two groups: penetrating and lamellar keratoplasty. Newer minimally invasive procedures have emerged over the years, to improve the visual outcome and reduce complications. This article summarizes the different procedures, their indications and complications, and outlines the pre-, peri- and postoperative management in a clinical setting.Corneal transplantation is the most commonly performed transplantation of donor tissue in modern medicine. In the last years a shift away from penetrating keratoplasty (PK) towards minimally invasive lamellar operative techniques, associated with less complications, can be observed. The Descemet membrane endothelial keratoplasty (DMEK) is used to treat endothelial corneal pathologies and has overtaken the PK to become the most commonly performed form of keratoplasty. Preparation and identification of possible risk-factors are essential preoperative steps to reduce peri- and postoperative complications of keratoplasties. If corneal graft rejection occurs, early and maximum therapy is crucial for graft survival. Laser-assisted techniques offer different advantages in lamellar and penetrating keratoplasty but are not very cost-efficient.

Accuracy of toric intraocular lens power calculation depending on different keratometry values using a novel network based software platform.

Purpose: To compare different corneal keratometry readings (swept-source-OCT-assisted biometry and Scheimpflug imaging) with a novel software platform for calculation of toric intraocular lenses. Setting: Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany. Design: Retrospective, non-randomized, clinical trial. Methods: Twenty-three eyes undergoing toric intraocular lens implantation were included. Inclusion criteria were preoperative regular corneal astigmatism of at least 1.00 D, no previous refractive surgery, no ocular surface diseases and no maculopathies. Lens exchange was performed with CALLISTO eye (Zeiss). For each patient, the expected postoperative residual refraction was calculated depending on three different corneal parameters of two different devices: standard K-front (K) and total keratometry (TK) obtained by a swept-source-OCT-assisted biometry system (IOL Master 700, Zeiss) as well as total corneal refractive power (TCRP) obtained by a Scheimpflug device (Pentacam AXL, Oculus). Barrett's formula for toric intraocular lenses was used for all calculations within a novel software platform (EQ workplace, Zeiss FORUM®). Results were statistically compared with postoperative refraction calculated according to the Harris dioptric power matrix. Results: The standard K values (mean PE 0.02 D ± 0.45 D) and TK values (mean PE 0.09 D ± 0.43 D) of the IOL Master 700 reached similar results (p = 0.96). 78% of eyes in both K and TK groups achieved SE within ±0.5 D of attempted correction and all eyes (100%) were within ±1.0 D of attempted correction in both groups. By contrast, the prediction error in the IOL calculation using the TCRP of the Scheimpflug device was significantly greater (mean PE -0.56 D ± 0.49 D; p = 0.00 vs. standard K and p = 0.00 vs. TK) with adjusted refractive indices. Thirty-nine and Ninety-one percentage of eyes in the TCRP group achieved SE within ±0.5 D (p = 0.008 K vs. TCRP and p = 0.005 TK vs. TCRP) and ± 1.0 D (p = 0.14 vs. TCRP) of attempted correction, respectively. Conclusion: All three corneal parameters (standard K, TK, TCRP) performed well in calculating toric IOLs. The most accurate refractive outcomes in toric IOL implantation were achieved by IOL calculations based on swept-source-OCT-assisted biometry. The SS-OCT-based K-front and TK values achieve comparable results in the calculation of toric IOLs.

One-stage versus two-stage bilateral implantable collamer lens implantation: a comparison of efficacy and safety.

Implantable collamer lens implantation (ICL) represents a safe and effective treatment for myopia and myopic astigmatism. To compare the outcomes of a bilateral one-stage same day approach to a two-stage approach, the databases of the University Eye Hospital Munich, Ludwig Maximilians-University and Smile Eyes Linz, Austria were screened for eyes that had undergone ICL implantation. Two-stage surgery was performed at an interval of 1 day (17 patients), 2 days (19 patients) and 1 week (2 patients). Variables analyzed were preoperative, 1-day and last follow-up uncorrected distance (UDVA) and corrected distance visual acuity (CDVA), manifest refraction, refractive spherical equivalent (SEQ), astigmatism, age, endothelial cell count (ECD), intraocular pressure (IOP) and ICL vaulting. In total, 178 eyes (100 eyes one-stage, 78 eyes two-stage) of 89 patients were included in this study. Mean follow-up was 1.1 ± 0.8 and 1.3 ± 0.5 years. Mean preoperative SEQ was - 7.9 ± 2.6 diopters (D) in the one-stage and - 8.0 ± 1.7 D in the two-stage group (p = 0.63) and improved to 0.00 ± 0.40 and - 0.20 ± 0.40 D at end of follow-up, showing slightly better stability in the one-stage group (p = 0.004). There was no difference in the efficacy (1.1 vs. 1.2, p = 0.06) and the safety index (1.2 vs. 1.2, p = 0.60) between the two groups. No eye (0%) in either group lost 2 lines or more of UDVA (p > 0.99). Refraction within ± 0.50 D and ± 1.00 D around target was achieved comparably often (89 vs. 86%, p = 0.65; 99 vs. 99%, p > 0.99). Endothelial cell loss was slightly higher in the two-stage group (1.3 vs. 4.3%). Vaulting at the final follow up was higher in the one-stage group (373.8 ± 205.4 µm vs. 260.3 ± 153.5 µm, p = 0.00007). There were no serious intraoperative complications in either group. In conclusion, this study demonstrates that both the one- and two-stage approaches are equally effective, predictable and safe. Regarding endothelial cell loss, vaulting and SEQ stability, the one-stage group showed slightly better outcomes, but these results are clinically questionable because they are so small. Larger studies are needed to quantitatively evaluate a potential benefit.

Intraocular lens power calculation using total keratometry and ray tracing in eyes with previous small incision lenticule extraction - A case series.

Purpose: To assess the IOL power calculation accuracy in post-SMILE eyes using ray tracing and a range of total keratometry based IOL calculation formulae. Observations: Ray tracing showed excellent predictability in IOL power calculation after SMILE and its accuracy was clinically comparable with the Barrett TK Universal II and Haigis TK formula. Conclusions and importance: Incorporating posterior corneal curvature measurements into IOL power calculation after SMILE seems prudent. The ray tracing method as well as selected TK-based formulae yielded excellent accuracy and should be favored in post-SMILE eyes.

Optimizing Refractive Outcomes of SMILE: Artificial Intelligence versus Conventional State-of-the-Art Nomograms.

PURPOSE: AI (artificial intelligence)-based methodologies have become established tools for researchers and physicians in the entire field of ophthalmology. However, the potential of AI to optimize the refractive outcome of keratorefractive surgery by means of machine learning (ML)-based nomograms has not been exhausted yet. In this study, we wanted to comprehensively compare state-of-the-art conventional nomograms for Small-Incision-Lenticule-Extraction (SMILE) with a novel ML-based nomogram regarding both their spherical and astigmatic predictability. METHODS: A total of 1,342 eyes were analyzed for creation of three different nomograms based on a linear model (LM), a generalized additive mixed model (GAMM) and an artificial-neuronal-network (ANN), respectively. A total of 16 patient- and treatment-related features were included. Each model was trained by 895 eyes and validated by the remaining 447 eyes. Predictability was assessed by the difference between attempted and achieved change in spherical equivalent (SE) and the difference between target induced astigmatism (TIA) and surgically induced astigmatism (SIA). The root mean squared error (RMSE) of each model was computed as a measure of overall model performance. RESULTS: The RMSE of LM, GAMM and ANN were 0.355, 0.348 and 0.367 for the prediction of SE and 0.279, 0.278 and 0.290 for the astigmatic correction, respectively. By applying the created models, the theoretical yield of eyes within ±0.50 D of SE from target refraction improved from 82 to 83% (LM), 84% (GAMM) and 83% (ANN), respectively. Astigmatic outcomes showed an improvement of eyes within ±0.50 D from TIA from 90 to 93% (LM), 93% (GAMM) and 92% (ANN), respectively. Subjective manifest refraction was the single most influential covariate in all models. CONCLUSION: Machine learning endorsed the validity of state-of-the-art linear and non-linear SMILE nomograms. However, improving the accuracy of subjective manifest refraction seems warranted for optimizing ±0.50 D SE predictability beyond an apparent methodological 90% limit.

Scleral Thickness as a Risk Factor for Central Serous Chorioretinopathy and Pachychoroid Neovasculopathy.

In the pathophysiology of central serous chorioretinopathy (CSC), scleral changes inducing increased venous outflow resistance are hypothesized to be involved. This work aims to investigate anterior scleral thickness (AST) as a risk factor for pachychoroid disorders. A randomized prospective case-control study was performed at the Ludwig Maximilians University, Department of Ophthalmology. In patients with CSC or pachychoroid neovasculopathy (PNV) and in an age- and refraction-matched control group, swept source optical coherence tomography (SS-OCT) was used to measure anterior scleral thickness (AST). Subfoveal choroidal thickness (SFCT) was assessed using enhanced depth imaging OCT (EDI-OCT). In total, 46 eyes of 46 patients were included in this study, with 23 eyes in the CSC/PNV and 23 eyes in the control group. A significantly higher AST was found in the CSC/PNV compared with the control group (403.5 ± 68.6 (278 to 619) vs. 362.5 ± 62.6 (218 to 498) µm; p = 0.028). Moreover, the CSC/PNV group showed a higher SFCT (392.8 ± 92.8 (191-523) vs. 330.95 ± 116.5 (167-609) µm, p = 0.004). Compared with the age- and refraction-matched controls, patients with CSC and PNV showed a significantly thicker anterior sclera. Scleral thickness might contribute to the venous overload hypothesized to induce pachychoroid phenotypes.

Optical coherence tomography-based misdiagnosis and morphological distinction in pachychoroid neovasculopathy vs. polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the rate of misdiagnosis of aneurysmatic pachychoroid type 1 choroidal neovascularization/polypoidal choroidal vasculopathy (PAT1/PCV) among cases diagnosed as non-aneurysmatic pachychoroid neovasculopathy (PNV) and to define optical coherence tomography (OCT) features facilitating their distinction. METHODS: The database of the Department of Ophthalmology, Ludwig-Maximilians University Munich, was screened for patients diagnosed with PNV. Multimodal imaging was screened for the presence of choroidal neovascularization (CNV) and aneurysms/polyps. Imaging features facilitating the diagnosis of PAT1/PCV were analysed. RESULTS: In total, 49 eyes of 44 patients with a clinical PNV diagnosis were included, of which 42 (85.7%) had PNV and 7 (14.3%) represented misdiagnosed PAT1/PCV. SFCT was comparable (PNV: 377 ± 92 vs. PAT1/PCV: 400 ± 83 µm; p = 0.39). Whereas no difference was detected in total pigment epithelium detachment (PED) diameter (p = 0.46), maximum PED height was significantly higher in the PAT1/PCV group (199 ± 31 vs. 82 ± 46, p < 0.00001). In a receiver operating characteristic (ROC) analysis, the optimum cutoff for defining "peaking PED" was 158 µm with an area under the curve of 0.969, a sensitivity of 1.0 (95% CI: 0.59-1.0), and a specificity of 0.95 (95% CI: 0.84-0.99). Sub-retinal hyperreflective material (SHRM; p = 0.04), sub-retinal ring-like structures (SRRLS; p < 0.00001), and sub-RPE fluid (p = 0.04) were significantly more frequent in eyes with PAT1/PCV. CONCLUSION: A relevant percentage of eyes diagnosed with PNV might instead suffer from PAT1/PCV. The detection of a maximum PED height ("peaking PED") exceeding approximately 150 µm, SHRM, SRRLS, and sub-RPE fluid might greatly aid in the production of a more accurate diagnosis.

Posterior Segment Involvement in Infantile Nephropathic Cystinosis - A Review.

Cystinosis is a rare lysosomal storage disease with a prevalence of 1 : 100 000 - 1 : 200 000 cases. It is caused by biallelic mutations in the CTNS gene, which encodes cystinosin, that transport cystine out of the lysosomes. Due to its dysfunction, cystine crystals accumulate in the lysosomes and ultimately cause apoptosis of the cell. Since cystinosin is ubiquitously present in the body, cystine crystals are deposited in every body structure and lead to the dysfunction of various organ systems in the course of time. Cystine crystals deposited in the cornea are a clinical hallmark of the disease, while there is less awareness of concomitant posterior segment alterations. Symmetrical pigment epithelial mottling and patches of depigmentation frequently start in the periphery and progress towards the posterior pole and can be encountered upon fundus biomicroscopy. Spectral-domain optical coherence tomography (SD-OCT) is an elegant tool for visualizing chorioretinal cystine crystals at the posterior pole. An SD-OCT-based clinical grading of the severity of the chorioretinal manifestation can potentially be applied as a biomarker for systemic disease status and for monitoring oral therapy adherence in the future. Along with previous histological examinations, it may also give information about the location of cystine crystals in the choroid and retina. This review aims to increase the awareness of vision-threatening retinal and choroidal changes in cystinosis and the concomitant findings in SD-OCT.

[Enhancement Options after Lens and Corneal Refractive Surgery]. / Enhancement-Optionen nach Linsen- und refraktiver Hornhautchirurgie.

BACKGROUND: Modern preoperative diagnostics as well as current surgical techniques allow cataract and refractive surgery to deliver precise refractive results.Occasionally, unsatisfactory refractive and visual results occur despite all the care taken. In these cases, subsequent improvement is required to achieve the best final visual outcome. This article shows the therapeutic options for the treatment of residual refractive errors after lens and corneal refractive surgery. KEY MESSAGES: The causes of postoperative refractive errors after refractive laser- or lens-based procedures are very diverse and require extensive workup of the cause as well as an individual solution to achieve the desired result. Before any further surgical intervention, specific complications of the primary procedure as well as concomitant ocular diseases must be excluded or treated. The appropriate enhancement after keratorefractive surgery depends primarily on the type of primary surgery, residual stromal thickness, possible complications from the initial surgery, and the patient's personal preference. For enhancements using surface treatments, such as PRK, the use of mitomycin C is recommended for prophylaxis of haze formation. After lens surgery, for low-grade postoperative refractive errors (spherical and astigmatic), keratorefractive enhancements provide the most accurate results. For higher refractive errors, lens-based procedures can be used, with add-on IOLs being safer and more precise compared with one IOL exchange. Low astigmatisms can be successfully treated with LRI or keratorefractive surgery, but higher astigmatisms should be corrected with an IOL exchange in the early postoperative period and with an add-on IOL in the later postoperative period. IOL explantations should be performed very cautiously, especially in cases of pronounced capsular fibrosis, previous posterior capsulotomy, and existing weakness of the zonular apparatus.

Corneal Manifestation in Patients with Infantile Nephropathic Cystinosis.

Nephropathic cystinosis is a rare autosomal recessive disease caused by mutations in the CTNS gene. This causes dysfunction of cystinosin, a protein that transports cystine out of lysosomes, causing cystine crystals to accumulate in cells in most organ systems. While renal complications predominate in the early forms of cystinosis, corneal crystal accumulation will inevitably manifest in all patients. The main symptoms are photophobia along with glare sensitivity and blepharospasm. In addition, corneal crystal accumulation can cause other complications, such as recurrent corneal erosions, punctate or filamentary keratopathy, and chronic dry eye. Eventually, peripheral corneal neovascularization and limbal stem cell deficiency may develop. Ophthalmologists play a key role in the early diagnosis of patients with cystinosis. This review aims to not only raise awareness of secondary complications of corneal crystal accumulation, but also to highlight current treatment options and challenges that ophthalmologists and pediatricians might face.

Comparison of Visual and Refractive Outcome between Two Methods of Corneal Marking for Toric Implantable Collamer Lenses (TICL) in Phakic Eyes.

PURPOSE: To compare the efficacy of digital-assisted reference marking for toric implantable collamer lenses (Callisto Eye System) with manual marking technique using a slit lamp markeur. METHODS: This study included patients that underwent implantation of a toric implantable collamer lens (EVO Visian toric ICL, Staar Surgical). Patients were included if they had a myopia above -3 diopters (D) and regular corneal astigmatism of 0.75 diopters or higher. Between both groups a 1:2 matching regarding similar preoperative level of myopia and astigmatism was performed. Visual and refractive outcomes were evaluated. Vector analysis was performed to evaluate total astigmatic changes. RESULTS: This study comprised 57 eyes of 57 patients with 19 eyes in the digital group and 38 eyes in the manual marking group. Postoperatively there were no statistically significant differences between both groups in UDVA (p = 0.467), spherical equivalent (SE) (p = 0.864), sphere (p = 0.761) and cylinder (p = 0.878). Vector analysis showed a slightly more accurate postoperative refractive astigmatism in the manual group (0.26 D at 107° ± 0.50 D) compared to the digital marking group (0.31 D at 107° ± 0.45 D), nevertheless with no statistically significant differences between both groups. CONCLUSIONS: A digital tracking approach for toric ICL alignment was an efficient and safe method for toric marking with similar results regarding visual and refractive outcomes compared to a conventional corneal marking method. Nevertheless, image-guided surgery helped to streamline the workflow in refractive ICL surgery.

Spectral domain optical coherence tomography-based retinochoroidal cystine crystal score: a window into infantile nephropathic cystinosis.

PRÉCIS: Cystinosis is a lysosomal storage disease leading to an accumulation of cystine crystals in several organs. We aim to comprehensively describe chorioretinal cystine crystals via spectral domain optical coherence tomography (SD-OCT) and elaborate a new biomarker for systemic disease control. BACKGROUND/AIMS: Cystinosis is a rare lysosomal storage disease leading to an accumulation of cystine crystals in several organs. This study aims to describe the deposition of retinochoroidal crystals in infantile nephropathic cystinosis and to elucidate their potential value as an objective biomarker for systemic disease control. METHODS: This cross-sectional study was carried out by the University Eye Hospital of the Ludwig-Maximilian University (Munich, Germany) in collaboration with the German Cystinosis Study Group. A complete ophthalmologic examination was performed, along with posterior segment SD-OCT (Spectralis; Heidelberg Engineering GmbH, Heidelberg, Germany). Retinochoroidal crystals were graded by employing a novel semiquantitative grading system-the retinochoroidal cystine crystal score (RCCCS). To quantify quality of vision, patients completed a specific questionnaire. A total of 85 eyes of 43 patients with cystinosis were included (mean age 22.3±8.8 years, range 6-39; male:female ratio=23:20). RESULTS: Cystine crystals were detectable in all neuroretinal layers and the choroid, most frequently in the choriocapillaris. The RCCCS was negatively correlated with cysteamine intake (r=0.533, p=0.001) and positively with cystatin C, a stable parameter of renal function (r=0.496, p=0.016). Moreover, the value of the RCCCS affected subjective quality of vision. Genetic analysis indicated pronounced crystal deposition in patients with heterozygous mutations containing the 57-kb-deletion allele of the CTNS gene. CONCLUSION: Ocular cystinosis leads to retinochoroidal crystal accumulation in every stage of the disease. Crystal deposition may be markedly influenced by oral cysteamine therapy. Therefore, the presented SD-OCT based grading system might serve as an objective biomarker for systemic disease control.