An 8‑year-old boy was presented for assessment of stromal crystalline corneal opacity in both eyes with increasing photophobia. Slit-lamp microscopy revealed anterior stromal, crystalline, ring-shaped corneal deposits in both eyes, with otherwise unremarkable corneal findings. Based on these findings, the patient was diagnosed with a juvenile form of Schnyder corneal dystrophy. Annual follow-up was performed over a period of 3 years. The family history revealed a case of Schnyder corneal dystrophy in the patient's grandmother. In cases of atypical crystalline, annular corneal opacities in children, Schnyder corneal dystrophy should be considered in the differential diagnosis. It should be noted that crystalline deposits are present in only 50% of all patients with this corneal dystrophy. The diagnosis can be particularly challenging in young patients as typical clinical signs, such as discoid stromal corneal opacity or arcus lipoides corneae, often do not appear until the third decade of life and early findings of corneal dystrophies in childhood are rarely described in the literature. In the present case, the positive family history facilitated the diagnosis. Excimer laser-assisted phototherapeutic keratectomy was discussed as a potential treatment option but was not desired by the family. Ein 8‑jähriger Junge stellte sich zur Mitbeurteilung einer stromalen kristallinen Hornhauttrübung an beiden Augen mit zunehmender Photophobie vor. Die spaltlampenmikroskopische Untersuchung zeigte anterior-stromale, kristalline ringförmige Hornhautablagerungen bei ansonsten unauffälligem Hornhautbefund an beiden Augen. Auf Grundlage dieser Befunde wurde die Diagnose einer juvenilen Form der Schnyder-Hornhautdystrophie gestellt. Der Patient wurde über einen Zeitraum von 3 Jahren jährlich kontrolliert. Die Familienanamnese ergab eine bekannte Schnyder-Hornhautdystrophie bei der Großmutter des Patienten. Bei untypischen kristallinen, ringförmigen Hornhauttrübungen im Kindesalter sollte differenzialdiagnostisch eine Schnyder-Hornhautdystrophie in Betracht gezogen werden. Es ist anzumerken, dass kristalline Ablagerungen nur in 50 % aller Patienten mit dieser Hornhautdystrophie vorhanden sind. Die Diagnosestellung kann insbesondere bei jungen Patienten erschwert sein, da typische klinische Zeichen wie eine diskoide stromale Hornhauttrübung oder ein Arcus lipoides häufig erst in der dritten Lebensdekade auftreten und frühe Befunde von Hornhautdystrophien im Kindesalter in der Literatur selten abgebildet werden. In dem hier beschriebenen Fall erleichterte die positive Familienanamnese die Diagnose. Eine Excimerlaser-assistierte phototherapeutische Keratektomie wurde als potenzielle Behandlungsoption diskutiert, jedoch von der Familie nicht gewünscht.

Schnyder corneal dystrophy (SCD) is a rare autosomal dominant condition characterized by the opacification of the cornea owing to the abnormal deposition of cholesterol. SCD-associated mutations have been identified in the gene encoding UbiA prenyltransferase domain-containing protein-1 (UBIAD1), which uses geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K2 subtype menaquinone-4 (MK-4). Beyond its enzymatic role, UBIAD1 serves as a key regulator of the endoplasmic reticulum (ER)-localized enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme in the mevalonate pathway that produces cholesterol and nonsterol isoprenoids such as GGpp and MK-4. Sterol-induced binding to UBIAD1 inhibits the sterol-accelerated ER-associated degradation (ERAD) of HMGCR to maintain the synthesis of nonsterol isoprenoids under conditions of cholesterol repletion. GGpp dissociates the HMGCR-UBIAD1 complex, triggering maximal ERAD of HMGCR and ER-to-Golgi translocation of UBIAD1. However, SCD-associated UBIAD1 resists this GGpp-induced dissociation and remains sequestered in the ER. ER retention of UBIAD1 leads to inhibition of HMGCR ERAD, promoting increased synthesis and accumulation of cholesterol. Here, chemical genetic screening was utilized to identify molecules that restored Golgi localization of SCD-associated UBIAD1 (N102S) and thereby relieve inhibition of HMGCR ERAD. We found that the chemotherapeutic tyrosine kinase inhibitor Apatinib stimulated ER-to-Golgi transport of both N102S and wild type UBIAD1. This effect required GGpp but was independent of Apatinib's tyrosine kinase inhibition. Apatinib-mediated Golgi transport of UBIAD1 enhanced the ERAD of HMGCR. Photoaffinity labeling studies indicated that Apatinib binds directly to UBIAD1, suggesting that the drug allosterically activates GGpp-induced transport of UBIAD1 from the ER to the Golgi.

We developed a comprehensive artificial intelligence DL model (CorneAI) to classify cataracts and corneal diseases into 9 categories. In this study, we aimed to enhance CorneAI by developing a deep learning (DL) model to diagnose the following conditions associated with corneal deposition: amyloidosis, band keratopathy, granular corneal dystrophy (GCD), lattice corneal dystrophy (LCD), gelatinous drop-like dystrophy (GDLD), Schnyder corneal dystrophy (SCD), and macular corneal dystrophy (MCD). We retrospectively analyzed 1546 slit-lamp images of 7 corneal opacities using You Only Look Once version 5 (YOLOv5). The model was trained with 5-fold cross-validation and tested on 303 images. DL model performance was compared with specialists and residents and evaluated. The positive predictive value (PPV) for all categories was 0.94 [95% confidence interval (CI): 0.93-0.96]. The highest PPVs for the individual diseases were relatively good, with 0.95 (0.93-0.97) for band keratopathy, 0.95 (0.94-0.97) for GCD, 0.83 (0.76-0.89) for LCD, 0.99 (0.97-0.99) for SCD, and 0.88 (0.65-0.96) for MCD. However, the PPVs for amyloid and GDLD were relatively low, at 0.75 (0.53-0.88) and 0.75 (0.46-0.91), respectively. When comparing DL model and human performance using a test dataset of 303 images, the PPVs were 0.96 (0.94-0.98) for our DL model, 0.89 (0.85-0.92) for specialists, and 0.67(0.61-0.72) for residents. Our DL model accurately diagnosed band keratopathy, GCD, LCD, SCD, and MCD although it was not precise enough to classify amyloidosis or GDLD. Although its performance first needs to be improved, this will be the first DL model to be installed in CorneAI for future.

Schnyder corneal dystrophy (SCD) is a rare, autosomal dominant, bilateral corneal dystrophy characterized by progressive deposition of cholesterol and phospholipids within the central corneal stroma. The condition is associated with pathogenic variants in the UBIAD1 gene, responsible for lipid metabolism. We report the case of a 17-year-old female presenting with progressive bilateral visual deterioration. Comprehensive ophthalmological examination, including slit-lamp biomicroscopy, in vivo confocal microscopy, and anterior segment optical coherence tomography (AS-OCT), was performed. The examination revealed bilateral stromal haze and central corneal crystalline deposits characteristic of SCD. The diagnosis required careful differentiation from other conditions presenting with corneal opacities or crystalline deposits, including other corneal dystrophies and systemic disorders affecting lipid metabolism. Early recognition through characteristic slit-lamp findings and multimodal imaging is decisive for appropriate management and monitoring of disease progression. Treatment options range from optical correction in early stages to phototherapeutic keratectomy, with corneal transplantation reserved for advanced cases. This case highlights the diagnostic value of combining clinical examination with in vivo confocal microscopy and AS-OCT in establishing the diagnosis of SCD, even when genetic testing is not performed.

Schnyder corneal dystrophy (SCD) is a rare autosomal dominant disorder characterized by bilateral corneal opacification due to abnormal cholesterol and phospholipid deposition. Mutations in the UBIAD1 gene, identified as causative in 2007, underline the condition, although its exact pathogenesis remains unclear. A 55-year-old female presented with persistent photophobia, blepharospasm, and corneal discomfort. She also reported joint pain related to rheumatoid arthritis (RA), managed with Ro-Actemra (tocilizumab). The ophthalmological evaluation revealed bilateral corneal stromal deposits resembling snowflakes, with visual acuities of 0.8 (right eye) and 0.7 (left eye). Multimodal imaging confirmed stromal hyperreflective deposits. Based on the clinical findings, SCD was diagnosed, although no genetic testing was performed. Symptomatic management with artificial tears was initiated. This case illustrates the diagnostic challenges of SCD, particularly in the absence of corneal crystals, a hallmark feature that is not universally present. Advanced imaging techniques aided diagnosis, and the coexistence of SCD and RA highlights the need for multidisciplinary care. Treatment options remain limited, although emerging therapies targeting oxidative stress and lipid metabolism show promise. This case highlights the importance of integrating ophthalmological and systemic care in SCD management and underscores the need for further research to expand diagnostic and therapeutic strategies for this rare disorder.