Ultraviolet A and Riboflavin Therapy for Corneal Ulcers
Ultraviolet A and Riboflavin Therapy for Corneal Ulcers
A 68-year-old insulin-dependent diabetic male patient presented with progressive pain, redness, photophobia, tearing, and decreased vision of 1-month duration in his left eye. He had history of cataract extraction and intraocular lens placement 5 years ago on his right eye. On examination, the visual acuities were counting fingers (CF)@3 ft in the right eye and CF@2 ft in the left eye, with no improvement on manifest refraction. The right eye was pseudophakic and had geographic atrophy because of age-related macular degeneration on fundus examination. On the left eye, the patient had conjunctival congestion and hyperemia, a central 2- × 2-mm corneal epithelial defect with deep stromal infiltration, endothelial plaque, moderate anterior chamber reaction, and vascularization extending from the limbus to the corneal infiltrate at 5-o'clock position (Fig. 1A). There was also a prominent nuclear opacification preventing ophthalmoscopy in the left eye. However, ultrasound examination revealed no pathology.
(Enlarge Image)
Figure 1.
Slitlamp photograph of the patient (A) showing a 2- · 2-mm central corneal epithelial defect with surrounding stromal infiltrate and conjunctival injection at initial presentation; (B) 2 weeks after the first ultraviolet (UV) A-riboflavin crosslinking (CXL) showing persistence of active infiltration of the stroma with stromal thinning next to the epithelial defect; (C) 1 week after the second UVA-riboflavin CXL showing resolution of the stromal infiltration; and (D) 6 months after the second UVA-riboflavin CXL showing complete central corneal scarring with no active infiltration or inflammation.
Corneal scrapings were performed twice for Gram and Giemsa staining and cultures; however, laboratory results were negative. The ulcer was unresponsive to extensive medical treatment with gentamicin gtt (14 mg/mL every hour (qs)), cefazolin gtt (50 mg/mL qs), fluconazole gtt (2 mg/mL qs), amphotericin B gtt (0.15 mg/mL qs), and ketoconazole (2 × 200 mg orally) administered for 10 days. Because the clinical appearance suggested fungal infection with a prominent ulceration, deep infiltrate, and an endothelial plaque, with no response to fortified therapy administered for 10 days, the patient was started a new regimen with topical voriconazole (0.01 mg/mL qs); amphotericin B and fluconazole drops were stopped. Intrastromal voriconazole (0.5 mg/mL) injection was performed once. A positive clinical response was noted on the fifth day of voriconazole treatment. However, the ulceration and infiltration was active again on the seventh day of voriconazole treatment, and stromal thinning was noted temporal to the deep stromal infiltrate.
Therefore, UVA-riboflavin CXL treatment was planned and performed as described by Wollensak et al. Briefly, the periocular area was cleaned with povidone-iodine solution. Proparacaine hydrochloride (0.5%) drops were administered, and an eye speculum was inserted. After topical anesthesia, the loose epithelium was removed. Ultrasound pachymetry was attempted to be performed; however, no measurement could be obtained. Riboflavin (Medio-Cross riboflavin/dextran solution, 0.1%) was topically administered for a period 30 minutes at an interval of 2 minutes. The cornea was then illuminated using a UV-X lamp (Peschke Meditrade GmbH, Huenenberg, Switzerland), UVA 365 nm, with an irradiance of 3.0 mW/cm and a total dose of 5.4 J/cm. Riboflavin was continued to be administrated to the cornea during UVA illumination.
Antifungal agents were continued after the UVA-riboflavin CXL therapy. The stromal infiltrate appeared inactive at 1-week follow-up examination, and the patient reported the improvement of his symptoms. However, reactivation was noticed again on the second week (Fig. 1B). A second UVA-riboflavin treatment was planned and performed 3 weeks after the first one. After the second treatment, the epithelial defect disappeared on day 7 (Fig. 1C), stromal infiltrate was inactive, corneal vascularization was distinctive, and the ulcer healed with a scar and prominent vascularization. The antimicrobial agents were tapered and stopped in 3 months. No activation of the ulcer was noted until the last follow-up examination at month 6, at which time the visual acuity was CF@4 ft, and there was complete scarring of the lesion (Fig. 1D).
Case Report
A 68-year-old insulin-dependent diabetic male patient presented with progressive pain, redness, photophobia, tearing, and decreased vision of 1-month duration in his left eye. He had history of cataract extraction and intraocular lens placement 5 years ago on his right eye. On examination, the visual acuities were counting fingers (CF)@3 ft in the right eye and CF@2 ft in the left eye, with no improvement on manifest refraction. The right eye was pseudophakic and had geographic atrophy because of age-related macular degeneration on fundus examination. On the left eye, the patient had conjunctival congestion and hyperemia, a central 2- × 2-mm corneal epithelial defect with deep stromal infiltration, endothelial plaque, moderate anterior chamber reaction, and vascularization extending from the limbus to the corneal infiltrate at 5-o'clock position (Fig. 1A). There was also a prominent nuclear opacification preventing ophthalmoscopy in the left eye. However, ultrasound examination revealed no pathology.
(Enlarge Image)
Figure 1.
Slitlamp photograph of the patient (A) showing a 2- · 2-mm central corneal epithelial defect with surrounding stromal infiltrate and conjunctival injection at initial presentation; (B) 2 weeks after the first ultraviolet (UV) A-riboflavin crosslinking (CXL) showing persistence of active infiltration of the stroma with stromal thinning next to the epithelial defect; (C) 1 week after the second UVA-riboflavin CXL showing resolution of the stromal infiltration; and (D) 6 months after the second UVA-riboflavin CXL showing complete central corneal scarring with no active infiltration or inflammation.
Corneal scrapings were performed twice for Gram and Giemsa staining and cultures; however, laboratory results were negative. The ulcer was unresponsive to extensive medical treatment with gentamicin gtt (14 mg/mL every hour (qs)), cefazolin gtt (50 mg/mL qs), fluconazole gtt (2 mg/mL qs), amphotericin B gtt (0.15 mg/mL qs), and ketoconazole (2 × 200 mg orally) administered for 10 days. Because the clinical appearance suggested fungal infection with a prominent ulceration, deep infiltrate, and an endothelial plaque, with no response to fortified therapy administered for 10 days, the patient was started a new regimen with topical voriconazole (0.01 mg/mL qs); amphotericin B and fluconazole drops were stopped. Intrastromal voriconazole (0.5 mg/mL) injection was performed once. A positive clinical response was noted on the fifth day of voriconazole treatment. However, the ulceration and infiltration was active again on the seventh day of voriconazole treatment, and stromal thinning was noted temporal to the deep stromal infiltrate.
Therefore, UVA-riboflavin CXL treatment was planned and performed as described by Wollensak et al. Briefly, the periocular area was cleaned with povidone-iodine solution. Proparacaine hydrochloride (0.5%) drops were administered, and an eye speculum was inserted. After topical anesthesia, the loose epithelium was removed. Ultrasound pachymetry was attempted to be performed; however, no measurement could be obtained. Riboflavin (Medio-Cross riboflavin/dextran solution, 0.1%) was topically administered for a period 30 minutes at an interval of 2 minutes. The cornea was then illuminated using a UV-X lamp (Peschke Meditrade GmbH, Huenenberg, Switzerland), UVA 365 nm, with an irradiance of 3.0 mW/cm and a total dose of 5.4 J/cm. Riboflavin was continued to be administrated to the cornea during UVA illumination.
Antifungal agents were continued after the UVA-riboflavin CXL therapy. The stromal infiltrate appeared inactive at 1-week follow-up examination, and the patient reported the improvement of his symptoms. However, reactivation was noticed again on the second week (Fig. 1B). A second UVA-riboflavin treatment was planned and performed 3 weeks after the first one. After the second treatment, the epithelial defect disappeared on day 7 (Fig. 1C), stromal infiltrate was inactive, corneal vascularization was distinctive, and the ulcer healed with a scar and prominent vascularization. The antimicrobial agents were tapered and stopped in 3 months. No activation of the ulcer was noted until the last follow-up examination at month 6, at which time the visual acuity was CF@4 ft, and there was complete scarring of the lesion (Fig. 1D).