Efficacy and Safety of Topical Cysteamine in Corneal Cystinosis: A Systematic Review and Meta-Analysis

Kaur, Sukhdeep; Sarma, Phulen; Kaur, Hardeep; Prajapat, Manisha; Shekhar, Nishant; Bhattacharyya, Jaimini; Kumar, Subodh; Medhi, Bikash; Ram, Jagat; Das, Dipankar; Avti, Pramod; Prakash, Ajay; Singh, Rahul; Bhattacharyya, Anusuya

doi:10.1016/j.ajo.2020.07.052

Cited by 9 publications

(8 citation statements)

References 17 publications

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“…Although, occurrences of local adverse events were more in the viscous formulation group, they were manageable. More trials with equivalent doses between the standard and viscous formulation to evaluate the comparative safety and efficacy are needed [16,107]. However, despite the low quality evidence, prospective observational studies suggest that cysteamine continues to be considered as a useful therapeutic strategy to delay ocular signs and symptoms associated with this systemic pathology [1].…”

Section: Current Situation and Future Perspectivesmentioning

confidence: 99%

“…Therefore, early initiation and adherence to topical therapy have a significant impact on disease progression [8]. Nowadays, although new prodrug strategies based on N-acyl or glutaric acid derivatives of cystamine have been researched [14,15], the aminothiol cysteamine remains the only available treatment of cystinosis [16]. It lowers intracellular levels of cystine by forming a cysteamine-cysteine mixed disulfide, which can egress the lysosome using the undamaged excretion pathway for lysine [17] (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

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Recent Research in Ocular Cystinosis: Drug Delivery Systems, Cysteamine Detection Methods and Future Perspectives

et al. 2020

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Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in different tissues and organs. Although renal damage prevails during initial stages, the deposition of cystine crystals in the cornea causes severe ocular manifestations. At present, cysteamine is the only topical effective treatment for ocular cystinosis. The lack of investment by the pharmaceutical industry, together with the limited stability of cysteamine, make it available only as two marketed presentations (Cystaran® and Cystadrops®) and as compounding formulations prepared in pharmacy departments. Even so, new drug delivery systems (DDSs) need to be developed, allowing more comfortable dosage schedules that favor patient adherence. In the last decades, different research groups have focused on the development of hydrogels, nanowafers and contact lenses, allowing a sustained cysteamine release. In parallel, different determination methods and strategies to increase the stability of the formulations have also been developed. This comprehensive review aims to compile all the challenges and advances related to new cysteamine DDSs, analytical determination methods, and possible future therapeutic alternatives for treating cystinosis.

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Section: Current Situation and Future Perspectivesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Recent Research in Ocular Cystinosis: Drug Delivery Systems, Cysteamine Detection Methods and Future Perspectives

et al. 2020

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Section: Introductionmentioning

confidence: 99%

“…Currently, the aminothiol cysteamine remains the only available treatment of cystinosis [ 8 ], although other pathways have been recently explored to expand therapeutic options [ 9 , 10 , 11 , 12 ]. Cysteamine lowers intracellular levels of cystine by forming a cysteamine–cysteine mixed disulfide, which resembles lysine and leaves the lysosome using a “lysine transport system” [ 8 , 13 ]. The authorization of oral cysteamine (Cystagon ® ) in 2012 by the Food and Drug Administration (FDA), followed by the delayed-release formulation years later (Procysbi ® ), has completely changed the management and prognosis of cystinosis [ 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Cysteamine Eye Drops in Hyaluronic Acid Packaged in Innovative Single-Dose Systems: Stability and Ocular Biopermanence

Castro-Balado

Bandín-Vilar²,

Cuartero-Martínez³

et al. 2022

Pharmaceutics

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Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in different tissues and organs causing, among other symptoms, severe ocular manifestations. Cysteamine eye drops are prepared in hospital pharmacy departments to facilitate access to treatment, for which vehicles that provide adequate biopermanence, as well as adaptable containers that maintain its stability, are required. Difficulties related to cysteamine preparation, as well as its tendency to oxidize to cystamine, show the importance of conducting rigorous galenic characterization studies. This work aims to develop and characterize an ophthalmic compounded formulation of cysteamine prepared with hyaluronic acid and packaged in innovative single-dose systems. For this task, the effect of different storage temperatures and the presence/absence of nitrogen on the physicochemical stability of the formulation and its packaging was studied in a scaled manner, until reaching the optimal storage conditions. The results showed that 0.55% cysteamine, prepared with hyaluronic acid and packaged in single-dose containers, is stable for 30 days when stored at −20 °C. In addition, opening vials every 4 h at room temperature after 30 days of freezing maintains the stability of the cysteamine formulation for up to 16 h. Moreover, ocular biopermanence studies were conducted using molecular imaging, concluding that the biopermanence offered by the vehicle is not affected by the freezing process, where a half-life of 31.11 min for a hyaluronic acid formulation stored for 30 days at −20°C was obtained, compared with 14.63 min for 0.9% sodium chloride eye drops.

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“…Recently, a viscous preparation of the topical cysteamine [Cystadrops (Recordati Rare Diseases)] has shown the ability to reduce corneal crystal load with a more manageable frequency of administration of just 4 times a day. 4 The ability to measure the amount and distribution of corneal crystals is important in assessing the efficacy of topically administered therapy for cystinosis. Various validated techniques have been applied to this end.…”

mentioning

confidence: 99%

Corneal Densitometry to Assess the Corneal Cystine Deposits in Patients With Cystinosis

Biswas

Alzahrani

Radhakrishnan

2022

Cornea

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Purpose:The purpose of this study was to assess the suitability of corneal densitometry measurements obtained with Scheimpflug imaging in estimating the corneal changes caused by cystine deposits in the cornea in patients with cystinosis.Methods:Scheimpflug imaging (Pentacam) was performed for 14 patients with cystinosis and 16 age-matched controls. Pentacam data were used for analysis of the corneal densitometry at different zones in the cornea for patients with cystinosis and controls. Densitometry measurements were compared with the corneal crystal scores obtained from the slitlamp images for patients with cystinosis.Results:There was no statistically significant difference in keratometry measurements between the 2 groups (P > 0.05). Corneal thickness was found to be significantly higher in the control group when compared with the cystinosis group (P = 0.0004). The mean corneal densitometry was significantly higher in patients with cystinosis when compared with controls at most of the corneal layers and zones. The corneal densitometry readings for the right and left eyes showed moderate positive correlation with the corneal crystal score with a ceiling effect being reached at the maximum corneal crystal score of 3.Conclusions:Corneal densitometry obtained through Pentacam can be used as an objective estimate of the level of cystine crystals present in patients with cystinosis. The clinical estimate of corneal crystal score, although effective at low levels of crystal deposition, does not allow for accurate estimates of change when the level of crystal deposition is high leading to limited utility when assessing treatment effects. Hence, densitometry measurements can potentially be used to assess treatment efficacy of cystinosis treatments in clinical settings.

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Efficacy and Safety of Topical Cysteamine in Corneal Cystinosis: A Systematic Review and Meta-Analysis

Cited by 9 publications

References 17 publications

Recent Research in Ocular Cystinosis: Drug Delivery Systems, Cysteamine Detection Methods and Future Perspectives

Recent Research in Ocular Cystinosis: Drug Delivery Systems, Cysteamine Detection Methods and Future Perspectives

Cysteamine Eye Drops in Hyaluronic Acid Packaged in Innovative Single-Dose Systems: Stability and Ocular Biopermanence

Corneal Densitometry to Assess the Corneal Cystine Deposits in Patients With Cystinosis

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