Findings
Classified as an orphan disease, neurotrophic keratitis (NK) is a rare degenerative corneal ailment with an elusive pathophysiology [1]. The disease progresses through three stages based on the severity of ocular surface damage; stage 1 involves mild epithelial alterations, superficial punctate keratopathy, and decreased corneal sensation [2]. Treatment strategies vary based on the stage of NK, ranging from topical therapies such as cenegermin, plasma rich in growth factors (PRGF-Endoret®) eye drops, and autologous serum tears, to more invasive approaches like corneal neurotization and transplantation [3]. While some studies advocate the beneficial effects of PRGF on advanced NK, limited data exists on its impact on stage 1 NK patients treated with PRGF eye drops [4]. This study is the first to investigate PRGF-Endoret® eye drops’ safety and efficacy in stage 1 NK.
This research, undertaken at the Bascom Palmer Eye Institute between November 2021 and December 2022, is a retrospective review of stage 1 NK patients who were administered PRGF eye drops 4–6 times daily over a 2-month period. We evaluated demographic data and multiple ocular surface clinical parameters pre- and post-treatment. The University of Miami Institutional Review Board approved this study. The captured data were analyzed using GraphPad Prism (Version 8).
Our study comprised 26 eyes from 15 patients: 53% were female and 73.3% displayed bilateral involvement. The average age was 76.3 ± 12.1 years, with a mean treatment duration of 2 ± 1.8 months. Leading causes included iatrogenic (26.7%), dry eye syndrome (26.7%), and herpes simplex virus (20%). PRGF treatment yielded notable improvements in several parameters; corneal sensitivity rose from 2.8 to 4.5 cm in 53.8% of eyes (p < 0.0001), tear breakup time increased from 3.6 to 5.0 s in 69.2% (p = 0.0007), and Schirmer’s score increased from 13.7 to 16.8 mm in 80.7% of eyes (p = 0.002). Furthermore, 80.7% of the eyes showed improved corneal staining (Fig. 1), 65.4% exhibited reduced MMP-9 levels, and 26.9% reported enhanced BCVA. Notably, there were no adverse events during the treatment. Patient characteristics and clinical data are summarized in Table 1.
Fig. 1. The initial and final status of two cases with stage 1 NK after 8.3 and 8.5 weeks of treatment with PRGF eye drops.
A, C Basal status, B, D final status of patient after PRGF treatment. Overall, 21 of 26 of the treated eyes (80.7%) showed improved corneal staining; among them, the mean Oxford staining scale before and after PRGF treatment was 2.48 and 0.95, respectively (P value = 0.006).
Table 1.
Demographic characteristics of stage 1 NK patients.
| Patient | Gender | Age range (years) | Eye involvement | Etiology of NK | Contact lens use | Previous ocular surgery | Mean V/A pre-T (Logmar) | Mean V/A post-T (Logmar) |
|---|---|---|---|---|---|---|---|---|
| 1 | F | 70 | Both | Iatrogenic (Glaucoma drops) | + | − | 0 | 0 |
| 2 | F | 80 | Left | Herpetic NK | + | − | 0.301 | 0.397 |
| 3 | F | 60 | Left | Herpetic NK | − | Cataract | 0.301 | 0.544 |
| 4 | M | 80 | Both | Dry eye syndrome | − | − | 0.176 | 0.301 |
| 5 | F | 70 | Both | Rosacea | − | − | 0.096 | 0.096 |
| 6 | M | 90 | Both | Fuch’s endothelial dystrophy | − | Cataract + Fuch’s surgery | 0 | 0.397 |
| 7 | F | 90 | Both | Herpetic NK | − | − | 0 | 0 |
| 8 | F | 70 | Both | Dry eye syndrome | − | Cataract+ Pterygium | 0.176 | 0.301 |
| 9 | F | 90 | Both | Dry eye syndrome | + | − | 0.477 | 0.096 |
| 10 | M | 70 | Left | Pseudophakic bullous keratopathy+ Iatrogenic (Glaucoma drops) | − | Multiple glaucoma surgeries | 1.096 | 1.096 |
| 11 | M | 90 | Both | Iatrogenic (Glaucoma drops) | − | − | 1.602 | 0.698 |
| 12 | F | 80 | Both | Dry eye syndrome | − | − | 0.397 | 0.301 |
| 13 | M | 50 | Left | Neurosurgical cause (meningioma) | + | − | 0 | 0 |
| 14 | M | 90 | Both | Previous vitrectomy+laser retinopexy | − | Radial keratotomy | 0.875 | 0.477 |
| 15 | M | 80 | Both | Iatrogenic (Glaucoma drops) | − | Cataract | 0.301 | 0.301 |
F female, M male, mean V/A initial mean visual acuity before PRGF treatment, mean V/A after mean visual acuity after PRGF treatment, Pre-T pre-treatment, Post-T post-treatment.
Managing and diagnosing NK is intricate due to various underlying ocular and systemic conditions [4]. Sanchez et al. reported favorable outcomes with PRGF for stage 2 and 3 NK patients, showcasing corneal defect resolution (99.4%) and BCVA improvement (52.8%) post 3 months of treatment [5]. Our findings align with these, revealing corneal healing in 80.7% of eyes and improved visual acuity in 26.9%. The lack of adverse reactions underscores the safety and efficacy of PRGF for all NK stages.
In conclusion, our study underscores the effectiveness of PRGF therapy in enhancing ocular surface parameters in stage 1 NK patients.
Author contributions
SG conducted the search, extracted data, and interpreted the results. KAO analyzed the data. ALS designed the review protocol and provided feedback. GA provided feedback on the report.
Funding
This work was supported by NIH Center Core Grant P30EY014801 (institutional), and Research to Prevent Blindness Unrestricted Grant GR004596 (institutional).
Data availability
The data that support the findings of this work are available from the corresponding author upon reasonable request.
Competing interests
Ocubio, LLC (ALS).
Ethics approval
Ethical approval was granted by the University of Miami Institutional Review Board, and the research adhered to the Declaration of Helsinki standards.
Footnotes
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
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Associated Data
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Data Availability Statement
The data that support the findings of this work are available from the corresponding author upon reasonable request.