الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 80 |  |  |
| | | from | 80 | | |
Abstract
Fungal keratitis is considered a serious potentially blinding corneal infectious disease. It was estimated to represent 20-60% of the cases with infective keratitis. Fungal keratitis due to Fusarium infection has a severe course with high risk of complication, and resistance to topical medications.
It is thought that PACK-CXL to be beneficial than medical, pharmaceutical antimicrobial therapy for bacterial and fungal keratitis. It has the advantage of treatment of mixed infections that is considered a challenging infection in most situations.
The aim of the present study is to investigate the efficacy of corneal collagen cross linking and to compare it with topical voriconazole treatment in fungal keratitis models experimentally induced in rabbit eyes based on clinical, microbiological and pathological analyses.
This is an interventional analytical study that was conducted in animal lab of Medical Research Institute, Alexandria University. The study includes 20 adult male New Zealand white rabbits. Fungal keratitis was induced in rabbits using 0.1 ml of prepared fusarium suspension injected intrastromal into the cornea of both eyes of all rabbits. The fusarium strain was acquired from culture of patient with fungal keratitis.
The rabbits were then divided into five groups (A, B, C, D and E), each group includes eight eyes of four rabbits. group (A) received no treatment and was left as control group. group (B) received topical Voriconazole (1 mg/mL) drops every hour between fourth and 10th days. Groups C, D, and E received a single corneal collagen cross linking session with application of riboflavin 0.1% drops every 5 minutes for 30 minutes, then high fluence UVA (30 mW/cm2) for 4 min 00 sec, 5 min 33 sec and 8 min 20 sec for group C, D and E respectively. The total UVA fluence was 7.2, 10.0 and 15.0 J/cm2 for group C, D and E respectively.
All eyes were observed daily for clinical signs of inflammation. At the end of the study (day 10), in each subgroup, after euthanasia, eyes of all rabbits were excised, corneal buttons of seven eyes were removed from the limbus for microbiological examination. One eye from each group was enucleated and sent to Pathology Department for pathological examination.
Regarding clinical signs recorded and evaluated through modified Schreiber scores, there were progression of the disease signs in group A (increase in the average modified Schreiber scores), while clinical improvement and decrease in average scores in groups B-E. One eye only in the control group complicated with corneal perforation and intraocular infection.
We found PACK-CXL alone can effectively suppress fungal infection and leads to improvement in the clinical manifestations of fungal keratitis. Significant clinical improvement can be seen while comparing all group of PACK-CXL treatment (group C, D, E) to control group (group A). Also, microbiological evaluation detected significant decrease in fungal CFU/ml for PACK-CXL treated groups in comparison to control group. In histopathological examination, PACK-CXL treatment groups show less inflammatory signs and lower hyphae density than control group.
Additionally, while comparing PACK-CXL treated groups to Voriconazole treated group (group B) we found both to be as effective in decreasing fungal infection, improving clinical manifestations with no clinically significant difference between them. This observation was also confirmed by microbiological and histopathological studies.
Many theories and mechanisms (146-148) were proposed to explain the role of CXL in management of fungal keratitis. One of those mechanisms attributed the damage to fungal elements to production of reactive oxygen species as a result of UVA reaction with the tissues. The reactive oxygen species lead to damage of fungal DNA/RNA. Another mechanism described is damage of fungal cell wall by riboflavin. On the other hand CXL leads to strengthening of corneal tissues preventing further fungal penetration into deeper tissues.
While comparing the use of different total delivered UVA in PACK CXL we noticed that increasing the total fluence of UVA is associated with better clinical and microbiological results. However the differences between the 3 groups are not statistically significant. This may be due to small sample size used. The pathological features of inflammation also witnessed more improvement with increasing UVA total fluence. On the other hand, no complications were reported with high UVA levels.
As a conclusion, we found that Using high fluence PACK-CXL (30 mW/cm2) is safe and effective as Voriconazole in the treatment of fungal keratitis. It decreases inflammatory signs, accelerates healing and decrease the incidence of corneal perforation and intraocular inflammation. Increasing the total fluence of UVA in PACK-CXL (total UVA fluence 7.2, 10.0 and 15.0 J/cm2) is associated with better outcomes. However, improvement of clinical signs with increased total UVA fluence is not statistically significant