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. 2020 Jun 17;2020(6):CD013001. doi: 10.1002/14651858.CD013001.pub2

Said 2014.

Study characteristics
Methods Study design: quasi‐randomized controlled trial, parallel group
Study center: Cornea Clinic of the Research Institute of Ophthalmology
Country: Egypt
Number randomized: 40 total, 21 in PACK‐CXL group, 19 in control group
Follow‐up period: daily follow‐up until complete healing
Exclusions and losses to follow‐up: none
Sample size calculation: not reported
Participants PACK‐CXL:

  • Total number randomized: 21

  • Age, mean (SD): 37.3 (NR)

  • Female, n (%): 13 (61.9)

  • Etiology: 7 (33.3%) bacterial, 3 (14.3%) fungal, 1 (4.8%) ameba, 10 (47.6%) other

  • Baseline BCVA: 2.16 ± 0.35

  • Baseline size of epithelial defect (mm²), mean (SD) or median (IQR): not reported

  • Baseline size of stromal infiltration (mm²), mean (SD) or median (IQR): not reported


Standard therapy (control):

  • Total number randomized: 19

  • Age, mean (SD): 49.8 (NR)

  • Female, n (%): 9 (47.4)

  • Etiology: 8 (42.1%) bacterial, 2 (10.5%) fungal, 2 (10.5%) ameba, 7 (36.8%) other

  • Baseline BCVA: 2.01 ± 0.44

  • Baseline size of epithelial defect (mm²), mean (SD) or median (IQR): not reported

  • Baseline size of stromal infiltration (mm²), mean (SD) or median (IQR): not reported


Overall:

  • Total number randomized: 40

  • Age, mean (SD): not reported

  • Female, n (%): 22 (55)

  • Etiology: 15 (37.5%) bacterial, 5 (12.5%) fungal, 3 (7.5%) ameba, 17 (42.5%) other

  • Baseline BCVA: not reported

  • Baseline size of epithelial defect (mm²), mean (SD) or median (IQR): not reported

  • Baseline size of stromal infiltration (mm²), mean (SD) or median (IQR): not reported


Group differences: mean size of the ulcer was larger in the PACK‐CXL group than in the control group
Inclusion criteria: aged > 18 years, seeking treatment at the Cornea Clinic of the Research Institute of Ophthalmology, infective corneal ulcer with a possible bacterial, fungal, Acanthamoeba, or mixed origin, evident corneal melting
Exclusion criteria: aged 18 years or younger, corneal ulceration in proximity (1 mm) to the corneal limbus, underlying autoimmune disease, history of herpetic eye disease, corneal thickness less than 400 micrometers with epithelium, or pregnancy or nursing
Interventions PACK‐CXL: initial antimicrobial therapy was done for both groups (see comparator group). Corneas thicker than 500 micrometers were deswelled using 70% glycerol drops applied topically at intervals of 2 to 3 seconds for 5 minutes. Iso‐osmolar riboflavin drops were instilled topically on the cornea every 2 minutes for over 30 minutes. Cornea was illuminated using UVX lamp at 365 nm ultraviolet A with an irradiance of 3 mW/cm² for 30 minutes and a total dose of 5.4 J/cm², during which riboflavin was instilled every 2 minutes and corneal pachymetry performed every 5 minutes. Antimicrobial treatment was continued as before and daily follow‐up examination was performed until healing was complete.
Standard therapy: initial antimicrobial therapy for both groups consisted of fortified vancomycin eye drops 50 mg/mL, fortified ceftazidime eye drops 50 mg/mL hourly, and the antifungal agent itraconazole 100 mg orally twice daily. Daily follow‐up examination was performed until healing was complete.
Outcomes Primary outcome:

  • slit lamp characteristics of corneal ulceration

  • corrected distance visual acuity

  • duration until healing

  • complications


Secondary outcome: not reported
Time points measured:

  • daily until healing was complete (defined as re‐epithelialization of the corneal epithelial defect with disappearance of hypopyon with no anterior chamber activity and clearing of stromal infiltrate)


Adverse effects related to PACK‐CXL for bacterial keratitis: "no severe complications occurred in the PACK‐CXL group"
Unit of analysis: eyes
Notes Enrollment period: 2010 to 2013
Funding source: not reported
Conflicts of interest: FH is co‐inventor of the PCT/CH 2012/000090 application (ultraviolet light source)
Trial registration: not reported
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) High risk Randomized using alternate allocation
Allocation concealment (selection bias) High risk Randomized using alternate allocation
Blinding of participants and personnel (performance bias)
All outcomes High risk As reported in the review protocol, the nature of surgical studies means that masking of participants is impossible. We therefore considered the overall review as at high risk of bias in this domain.
Blinding of outcome assessment (detection bias)
All outcomes Unclear risk Not reported
Incomplete outcome data (attrition bias)
All outcomes Low risk All outcome data available.
Selective reporting (reporting bias) Low risk The Research Institute of Ophthalmology Institutional Review Board approved the study protocol.
Other bias Unclear risk 1 of the study authors is a co‐inventor of an ultraviolet light source.

PACK‐CXL: Photoactivated chromophore for collagen cross‐linking; SD: Standard deviation; NR: Not reported; BCVA: Best corrected visual acuity; IQR: Interquartile range; UVA: Ultraviolet A; BPVA: Best pinhole‐corrected visual acuity