Introduction
Cystinosis is a rare autosomal recessive lysosomal storage disorder characterized by the accumulation of cystine crystals within various tissues due to a defect in the CTNS gene, which encodes the lysosomal cystine transporter. This condition typically manifests in three forms: nephropathic (infantile), intermediate (juvenile), and non-nephropathic (adult or ocular), each varying in severity and the age of onset [ 1 , 2 ]. Ocular involvement, particularly corneal crystal deposition, is a hallmark of cystinosis and is most commonly observed in patients with the non-nephropathic variant.
This case report discusses a 37-year-old male presenting with ocular cystinosis. While ocular cystinosis is predominantly associated with childhood diagnosis, the presentation in adulthood underscores the spectrum of disease progression and its diagnostic challenges. Key features include photophobia, foreign body sensation, and the characteristic corneal crystal deposits, often leading to a delayed diagnosis if systemic symptoms are absent [ 3 ]. Through this report, we aim to highlight the clinical manifestations, diagnostic approach, and management considerations for ocular cystinosis, emphasizing its relevance in adult patients and the importance of interdisciplinary care for optimal outcomes.
Case Presentation
A 37-year-old Indian male from Pune and Hindu by religion presented to the ophthalmology outpatient clinic with a 6-month history of persistent redness and photophobia in both eyes. He denied any associated symptoms such as pain or decreased vision and had no significant past medical or ocular history. There was no history of any long-term medication usage. He reported no systemic illnesses. He was born to non-consanguineous parents, and there was no family history of similar conditions or any known familial inheritance/diseases.
On examination, his visual acuity was 6/6 in both eyes. A detailed slit-lamp examination of both eyes revealed fine, crystal-like deposits scattered all throughout the cornea with no signs of inflammation ( Fig. 1 a, b) ( Fig. 2 a, b). The rest of the anterior segment findings and intraocular pressure was within normal limits. Posterior segment examination was done with indirect ophthalmoscope and 20D lens and was also within normal limits, ruling out Bietti’s crystalline dystrophy.
Anterior segment optical coherence tomography (AS-OCT) images of both eyes were done, and it showed multiple hyperreflective lesions distributed throughout the corneal stroma, representing cystine crystal deposits. In both the right and left eyes, the crystals were primarily located in the anterior and mid-stromal layers. The corneal architecture was otherwise preserved, with no evidence of stromal thinning, edema, or disruption of the epithelial or endothelial layers ( Fig. 3 a, b).
The patient underwent a comprehensive systemic evaluation to rigorously exclude alternative etiologies of bilateral stromal corneal crystals. Renal function tests, liver function tests, and a metabolic panel were done, all of which were within normal limits ruling out any metabolic/storage disorders. Serum creatinine level was 0.87 mg/dL, with normal electrolytes, blood counts, and urinalysis findings, effectively ruling out systemic (nephropathic) involvement and hematologic malignancies. Leukocyte cysteine levels were within normal limits (<0.2 nmol). Urine Bence Jones protein was undetected ruling out multiple myeloma. Lipid profile was within the normal range ruling out Schnyder corneal dystrophy.
The patient was started on topical cysteamine 0.44% ophthalmic solution, prescribed every hour while awake to reduce the corneal cystine crystal load and relieve symptoms of photophobia. He was also advised to use lubricating eye drops and wear tinted lenses for additional comfort. The patient was followed up once every month for a year to monitor the effect of cysteamine ophthalmic solution on crystal progression. Since systemic evaluation revealed no signs of renal or metabolic involvement, systemic cysteamine was not initiated. Genetic testing for CTNS mutations was considered to confirm the diagnosis and aid in long-term management planning, but the patient refused to do so. The patient was counseled regarding the chronic nature of the condition and the importance of adherence to lifelong topical therapy to maintain good visual function and avoid recurrence of symptoms.
The patient noted that following the prescribed topical cysteamine regimen and supportive measures markedly improved his comfort and alleviated photophobia, enabling him to carry out daily activities without visual discomfort. He felt reassured by the regular monitoring, which allowed him to see the effects of treatment and emphasized the importance of adherence. He also valued the comprehensive care approach, including guidance on managing a chronic condition, which positively impacted his quality of life and self-confidence.
Discussion
This case highlights the importance of considering ocular cystinosis in adults presenting with bilateral corneal crystals and minimal or no systemic involvement. A high index of suspicion, especially in patients with subtle symptoms and preserved vision, is crucial for early diagnosis. Prompt initiation of topical cysteamine therapy can prevent progression of corneal pathology, alleviate symptoms, and improve quality of life. The case also underscores the role of interdisciplinary collaboration, involving ophthalmology and nephrology, to ensure a holistic approach to patient care and surveillance.
A rigorous stepwise evaluation was undertaken to systematically exclude alternative etiologies of bilateral stromal corneal crystals, including hereditary dystrophies, systemic metabolic or storage disorders, hematologic malignancies, and drug-induced keratopathies. Objective evaluation using slit-lamp biomicroscopy and AS-OCT confirmed the presence of bilateral, anterior and mid-stromal hyperreflective deposits, allowing precise documentation of crystal burden and distribution. Comprehensive systemic evaluation, including renal and liver function tests, serum electrolytes, lipid profile, leukocyte cystine levels, and hematologic studies, effectively excluded nephropathic cystinosis, metabolic disorders, and paraproteinemias, reinforcing the diagnosis of isolated ocular cystinosis.
Cystinosis is a rare autosomal recessive lysosomal storage disorder characterized by the defective transport of cystine across the lysosomal membrane due to mutations in the CTNS gene, which encodes the cystine transporter, cystinosin [ 4 ]. The resultant accumulation of cystine leads to the formation of crystals that disrupt normal cell function in various organs, including the kidneys, eyes, thyroid, pancreas, and muscles. Cystinosis has an estimated incidence of 1 in 100,000–200,000 live births, with three recognized clinical forms: nephropathic (infantile), intermediate (juvenile), and non-nephropathic (ocular) [ 1 ].
The nephropathic form, the most severe, typically manifests within the first year of life with symptoms such as failure to thrive, polyuria, dehydration, and features of Fanconi syndrome. If untreated, these patients often progress to end-stage renal disease by the end of the first decade [ 3 ]. The intermediate form presents later in childhood or adolescence with milder renal involvement and slower progression [ 1 ]. In contrast, the non-nephropathic (ocular) variant, often referred to as adult-onset cystinosis, is primarily limited to the eye. These patients have normal renal function and typically present later in life with subtle ocular complaints [ 5 ].
The hallmark of ocular cystinosis is corneal crystal deposition, which usually begins in the peripheral corneal stroma and progressively involves the central cornea over time. The deposition of cystine crystals in the avascular corneal tissue leads to a range of symptoms, including photophobia, foreign body sensation, ocular irritation, and in advanced cases, punctate keratopathy or recurrent epithelial erosions [ 6 ]. These symptoms may be mistakenly attributed to dry eye or allergic conjunctivitis, especially when systemic features are absent, often resulting in delayed diagnosis. Despite the presence of crystals, visual acuity typically remains preserved in the early stages, although advanced disease may lead to corneal scarring and visual impairment [ 6 ].
On slit-lamp biomicroscopy, these crystals appear as glistening, refractile, needle-shaped opacities, arranged in a radial or fan-like pattern throughout the corneal stroma. OCT can aid in the diagnosis by showing hyperreflective particles in the anterior and mid-stromal layers. In vivo confocal microscopy provides high-resolution images of the deposits and is useful for assessing the burden and distribution of crystals [ 7 ]. The conjunctiva, iris, and lens may also harbor crystals, although these are less commonly symptomatic. Posterior segment findings are rare in ocular cystinosis but may include depigmentation with pigmentary mottling, macular abnormalities, bone spicules, and pigment clumps resembling retinitis pigmentosa [ 3 , 8 , 9 ].
Cystinosis should be considered in any child with growth failure and signs of renal Fanconi syndrome as it is the most common inherited cause. Diagnosis relies on measuring elevated intracellular cystine, preferably in PMN leukocytes due to their higher sensitivity. Modern methods like tandem mass spectrometry are now favored over older techniques such as the cystine-binding assay, due to improved sensitivity and safety. Laboratories should establish their own reference ranges, and in Europe, quality control is overseen by the ERNDIM. Genetic testing of the CTNS gene enables early and prenatal diagnosis, with a 57-kb deletion being the most common mutation in Northern Europe. Although truncating mutations usually correlate with the severe infantile form, exceptions to genotype-phenotype patterns have been observed [ 10 , 11 ]. Given the genetic basis of the disease, genetic counseling is also advised, especially in populations where consanguinity is common. In suspected cases of isolated ocular cystinosis in adulthood, family screening may uncover undiagnosed cases or carrier states.
Treatment primarily involves the use of topical cysteamine hydrochloride ophthalmic solution, the only approved therapy that reduces corneal cystine crystal accumulation. Cysteamine enters lysosomes and reacts with cystine to form cysteine and a cysteine-cysteamine mixed disulfide, both of which can exit the lysosome via intact transporters [ 12 ]. However, due to its short half-life, cysteamine ophthalmic solution must be instilled frequently (up to 6–12 times daily), which poses a significant compliance burden. It is important to note that while oral cysteamine is effective in treating systemic manifestations of nephropathic cystinosis, it does not reach therapeutic levels in the avascular cornea, making topical therapy essential in ocular or isolated presentations [ 4 , 12 ]. Patients require long-term monitoring to assess treatment efficacy, detect potential complications such as band keratopathy, and ensure no systemic involvement develops later in life.
Bilateral, diffuse stromal corneal crystals are a distinctive finding with a broad differential encompassing hereditary corneal dystrophies, systemic metabolic/storage disorders, paraproteinemias, blood dyscrasias, and drug-related causes. The classic diagnosis is Schnyder corneal dystrophy, an autosomal dominant disorder with cholesterol and phospholipid deposition in the corneal stroma, often associated with systemic lipid abnormalities. Other metabolic disorders, such as primary hyperoxaluria, tyrosinemia type II, and homocystinuria, may occasionally present with crystalline corneal changes. Multiple myeloma, monoclonal gammopathy of undetermined significance, and Waldenström macroglobulinemia can all cause crystalline keratopathy due to deposition of immunoglobulin light chains or cryoglobulins in the cornea. Similarly, chronic lymphocytic leukemia and lymphoplasmacytic disorders have been reported to produce corneal crystal deposition, highlighting the need to evaluate for hematological malignancy in adults with new-onset bilateral crystalline keratopathy. Several corneal dystrophies beyond Schnyder may also present with crystalline deposits. Lattice corneal dystrophy produces refractile amyloid deposits, and granular corneal dystrophy type II (Avellino dystrophy) may show a mixture of hyaline and amyloid deposits. Bietti crystalline dystrophy, while primarily a retinal dystrophy, can show limbal corneal crystals. Drug-induced crystalline keratopathy is another recognized entity. Long-term use of tamoxifen, indomethacin, cysteamine, and antimalarials like chloroquine/hydroxychloroquine can produce crystalline stromal or subepithelial deposits. Careful systemic history, hematologic evaluation, and genetic workup are crucial for accurate diagnosis and management.
Multiple studies and case reports have described the ocular manifestations of cystinosis, and their key findings are summarized (shown in Table 1 ) [ 3 , 5 , 13 – 17 ]. This case shares several features with previously reported cases of cystinosis. Corneal cystine crystal deposition was a consistent finding, evident on slit-lamp and AS-OCT. Similarities include bilateral involvement, stromal localization of crystals primarily in the anterior and mid-stroma layers, and visibility as hyperreflective, birefringent lesions on slit-lamp and AS-OCT. Like mild or early-stage nephropathic cases and ocular-only cases, the corneal architecture in this patient is preserved, visual acuity is normal, and there is no evidence of stromal disruption or systemic involvement. While the severity and progression vary across published reports, this patient’s deposits mirror the typical morphology, distribution, and imaging characteristics described in the literature, representing a classic presentation of ocular cystinosis with non-nephropathic features. Similar to previous reports, the patient experienced photophobia and showed symptomatic improvement with topical cysteamine therapy, with regular slit-lamp follow-up allowing monitoring of corneal crystal progression. In contrast to most cases of infantile or juvenile nephropathic cystinosis, which often involve systemic manifestations such as renal impairment or metabolic disturbances, this patient had isolated ocular involvement, preserved visual acuity, and no posterior segment abnormalities. Additionally, while genetic confirmation was performed in many studies, it was not obtained here due to patient refusal, making this a clinically diagnosed, adult-onset ocular cystinosis case [ 13 – 17 ].
Table 1.
Summary of a few studies on ocular cystinosis
| Author and year | Population/case | Key ocular findings | Significance |
| Keidel et al. [ 13 ] (2020) | Cystinosis patients vs. controls | Hyperreflective stromal crystals (anterior, posterior, or full thickness) | OCT thresholds objectively quantify crystal load; biomarker for monitoring progression/therapy |
| Tsilou et al. [ 3 ] (2007) | Adult with infantile cystinosis | Corneal crystals, pigmentary retinopathy, band keratopathy, CNV | Shows progressive disease despite treatment; histopathology confirmed widespread deposits |
| Kowalczyk et al. [ 14 ] (2020) | 7 patients (infantile and juvenile) | Corneal crystals in all | Early diagnosis and follow-up prevent complications; topical cysteamine safe |
| Helmi et al. [ 15 ] (2019) | 22-year-old woman, infantile type | Progressive corneal crystals, glaucoma, uveitis, vitreous hemorrhage, vision loss | Severe asymmetric involvement despite therapy; need for vigilant monitoring |
| Choudhary et al. [ 16 ] (2025) | 4-year-old girl, infantile + CKD | Bilateral crystals, papilledema, retinal deposits | Importance of multidisciplinary care; systemic + topical therapy |
| Razzak et al. [ 17 ] (2024) | 5-year-old boy with systemic disease | Dense corneal crystals, conjunctival deposits, normal retina | Early systemic + topical cysteamine improved symptoms and stabilized disease |
| Anikster et al. [ 5 ] (2000) | 4 cases of ocular non-nephropathic cystinosis | Corneal crystals without renal disease | CTNS mutations with residual activity → ocular-only phenotype |
This case report has few limitations. First, as it describes a single patient, the findings cannot be generalized to the wider population with ocular cystinosis. The absence of confirmatory CTNS gene mutation analysis restricts the molecular validation of the diagnosis, which is especially important in atypical or adult-onset cases. Without molecular confirmation, it is more difficult to explain why cystinosis presented so late in life, and the absence of genetic confirmation limits the strength of the case. Advanced diagnostic tools such as in vivo confocal microscopy and Pentacam Scheimpflug platform were not employed, which could have provided more precise characterization of crystal deposition and ocular surface health. Lastly, due to the rarity of the condition, comparative analysis with other similar cases was not possible.
Conclusion
This case highlights the importance of recognizing ocular cystinosis as a distinct clinical entity that can present in adulthood, often in the absence of systemic involvement. The presence of characteristic corneal crystal deposits, even in a patient with normal vision and no systemic symptoms, should prompt consideration of this rare diagnosis. Early detection through slit-lamp examination and supportive imaging such as anterior segment OCT allows for timely initiation of topical cysteamine therapy, which can prevent progression and reduce patient discomfort. A multidisciplinary approach, including genetic evaluation and periodic systemic screening, is essential to ensure comprehensive care. Awareness among clinicians of such atypical presentations can help avoid diagnostic delays and improve long-term ocular outcomes.
Statement of Ethics
Ethical approval is not required for this study in accordance with local or national guidelines. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000548833 ).
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
Funding Sources
This study was not supported by any sponsor or funder.
Author Contributions
Aishwarya, Kalibo, Iqra, and Saujas: contributions to the conception or design of the work; the acquisition, analysis, or interpretation of data for the work, and drafting the work or reviewing it critically for important intellectual content.
Funding Statement
This study was not supported by any sponsor or funder.
Data Availability Statement
The data that support the findings of this study are not publicly available due to privacy reasons but are available from the corresponding author upon reasonable request.
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Associated Data
Supplementary Materials
Data Availability Statement
The data that support the findings of this study are not publicly available due to privacy reasons but are available from the corresponding author upon reasonable request.