Anterior Segment Herpetic Keratitis
Table 1: Key Studies Supporting the Use of Ganciclovir in Herpes Simplex Keratitis Study Type
Number of Patients and Centers
Phase II parallel group, 67 pts ≥12 years of age
randomized, comparative, with HSK at four centers multicenter study
in Africa Dendritic (51) or geographic (16) epithelial keratitis
Treatments—GCV and Comparator
Pts treated with 0.15% GCV Efficacy Findings For GCV 0.15%, GCV 0.05%,
gel (n=23), 0.05% GCV (n=22), and ACV 3%, healing rates or 3% ACV (n=22) five times daily until ulcer healed then
were 82.6, 77.3, and 72.7%. Investigator assessments of
three times daily for one week efficacy as very satisfactory (on day 14)—71.43, 66.67, and 52.63% (ns).
Conjunctival samples showed an identical rate of viral elimination in GCV 0.15% and ACV 3%, but GCV 0.05% was less effective
Phase II parallel group 37 pts ≥18 years with HSK Pts treated with 0.15% GCV
then three times daily for one week
For GCV 0.15% and ACV 3%,
randomized, comparative, at four centers in France. (n=19) or ACV 3% (n=18) five respectively, healing rates multicenter study
Dendritic (36) or geographic times daily until ulcer healed were 83.3 and 70.6% (ns). (one) epithelial keratitis
For GCV 0.15% and ACV 3% groups 38.5 and 76.9% of
pts experienced blurred vision
Withdrawals due to worsening for >5 minutes. For GCV 0.15% ulcer or complications were 11.1 and 41.2% (p=0.06).
Phase II parallel group, 109 pts ≥5 years with HSK at Pts treated with 0.15% GCV
randomized, comparative, one center in Pakistan. single center study
Dendritic or geographic epithelial keratitis
Median time of healing was six ‘excellent’. For ACV 3% these days for GCV 0.15% and seven were 75 and 67%8,29 days for ACV 3% (p=0.056) For GCV 0.15%, GCV 0.05%,
gel (n=36), 0.05% GCV (n=35), and ACV 3%, respectively, or 3% ACV (n=38) five times daily for 10 days
healing rates were 86.1, 80, and 71.1% (ns). Withdrawals due to
complications were 5.6, 11.4, and 21.05% (p=0.02)
Stromal damage in withdrawals occurred in 50, 50, and 62.5% of pts
Phase III parallel group 164 pts at 28 centers in
or geographic (26) epithelial keratitis
Pts treated with 0.15% GCV
times daily until ulcer healed then three times daily for one week
Dendritic ulcers (n=137) and
randomized, comparative, Europe. Dendritic (138) or (n=84), or ACV 3% (n=80), five geographic ulcers (n=27) multicenter study
were reported separately. In dendritic ulcers treated with GCV 0.15% and ACV 3%, respectively, healing rates were 88.7 and 91% (ns). Both groups showed similar rates of withdrawals (ns)
At Day 14, fewer subjects in the GCV 0.15% group reported a stinging or burning sensation than in the ACV 3% group (p=0.03). The rate of punctate keratitis was lower in the GCV 0.15% group. The proportions of pts (p=0.0002) and
investigators (p=0.00006) rating the tolerance to the product as excellent were significantly greater for the GCV 0.15% group than the ACV 3% group8,22
ACV = acyclovir; GCV = ganciclovir; HSK = herpes simplex keratitis; Pts = patients; ns = non significant.
was significantly higher in the GCV group (78.7%) compared with the ACV group (43.94%) treated for dendritic ulcers. Similarly, patients reported that the overall tolerance with GCV was more frequently considered excellent (75.36%) compared with ACV (42.42%).8 greater level of compliance amongst patients.
This may result in a
There is discussion amongst physicians that GCV 0.15% gel could be suitable for eyelid application/nasal ulcerations. However, in the US, this recommendation is not included in the package insert, and is therefore
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described as off-label, non-FDA approved use. However, since GCV gel is approved for ocular use it is likely to be safe for use on eyelids or for nasal ulcerations. The use of GCV for this indication has not yet been clinically tested and the FDA does not give approval unless there are clinical trial data in support of a treatment. Currently there are no clinical studies which address whether 0.15% GCV gel can be used for the prophylactic management of corneal ulcerations. However, the Herpetic Eye Disease study (HEDS) to investigate the effect of oral acyclovir therapy for recurrences of HSV epithelial keratitis and stromal keratitis
US OPHTHALMIC REVIEW
100% of investigators and 100% of pts rated general tolerance as
Safety Findings
GCV 0.15 and 0.05% were well tolerated—stinging and burning sensations were less common than ACV 3% (p=0.10). Rates of toxic superficial punctate keratitis were similar in all three groups (ns)8,29
Tolerability was acceptable for all three groups. The incidence of superficial punctate keratitis cases appearing or exacerbated by treatment was similar for all three groups. No hematological effects observed8
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