patients aged more than 18 years with a diagnosis of active hsv nsk were enrolled .
ulcer measuring more than 2 mm and involving more than one - third of corneal stroma with an overlying epithelial defect were included .
patients were excluded if they had been treated with antiviral therapy and/or topical or systemic steroids within the previous 6 weeks .
culture positive bacterial , fungal , or parasitic infections and patients with known allergy to oral or topical acyclovir were excluded from the study .
pregnant and lactating women and patients with renal insufficiency were also excluded from the study .
patients who had undergone corneal surgery or any ocular surgery in the preceding 6 months were also excluded .
the patients were classified as early presentation when the duration of disease was less than 6 weeks and as late presentation when more than 6 weeks duration .
history of recurrent episodes of keratitis , any exacerbating or precipitating factors , and any associated systemic illness was recorded .
the diagnosis of nsk was clinically based on the presence of thinning , ulceration , and dense infiltration of the stroma , accompanied by an overlying epithelial defect with minimal discharge .
patient 's symptoms , visual acuity , conjunctival injection , stromal edema , size of infiltration , and severity of corneal thinning were evaluated on every visit .
complete ophthalmic examination was performed by a single cornea specialist at baseline , day 3 and every week thereafter until 10 weeks .
patients received a 10 weeks regimen of oral acyclovir 400 mg 5 times / day ( acivir , cipla ltd , india ) and topical acyclovir eye ointment 5 times / day ( acivir , cipla ) for 2 weeks .
diluted topical prednisolone sodium phosphate eye drops in buffered isotonic aqueous solution ( 0.125% predforte , allergan , irvine , ca , usa ) was commenced in tapering doses ( starting dose of 4 times / day ) .
primary outcome measure was a response to therapy which was clinically assessed by comparing the size of infiltrate at trial entry and after 2 weeks of systemic and topical antiviral treatment .
secondary outcome measure was improvement in best - corrected visual acuity from baseline to end of 10 weeks .
any surgical intervention or adverse incident occurring during the course of therapy was recorded to assess safety of the treatment .
treatment failure was considered in cases where there was an increase in the area of infiltrate , appearance of fresh infiltrate , < 10% decrease in the stromal keratitis or corneal perforations requiring keratoplasty within first 2 weeks .
cyanoacrylate tissue adhesive application for management of extreme thinning was noted as a surgical intervention .
however , these patients continued to remain in the study and response to therapy was recorded .
prospective interventional case series conducted at a tertiary eye care hospital from april 2013 to april 2014 .
patients aged more than 18 years with a diagnosis of active hsv nsk were enrolled .
ulcer measuring more than 2 mm and involving more than one - third of corneal stroma with an overlying epithelial defect were included .
patients were excluded if they had been treated with antiviral therapy and/or topical or systemic steroids within the previous 6 weeks .
culture positive bacterial , fungal , or parasitic infections and patients with known allergy to oral or topical acyclovir were excluded from the study .
pregnant and lactating women and patients with renal insufficiency were also excluded from the study .
patients who had undergone corneal surgery or any ocular surgery in the preceding 6 months were also excluded .
the patients were classified as early presentation when the duration of disease was less than 6 weeks and as late presentation when more than 6 weeks duration .
history of recurrent episodes of keratitis , any exacerbating or precipitating factors , and any associated systemic illness was recorded .
the diagnosis of nsk was clinically based on the presence of thinning , ulceration , and dense infiltration of the stroma , accompanied by an overlying epithelial defect with minimal discharge .
patient 's symptoms , visual acuity , conjunctival injection , stromal edema , size of infiltration , and severity of corneal thinning were evaluated on every visit .
complete ophthalmic examination was performed by a single cornea specialist at baseline , day 3 and every week thereafter until 10 weeks .
patients received a 10 weeks regimen of oral acyclovir 400 mg 5 times / day ( acivir , cipla ltd , india ) and topical acyclovir eye ointment 5 times / day ( acivir , cipla ) for 2 weeks .
diluted topical prednisolone sodium phosphate eye drops in buffered isotonic aqueous solution ( 0.125% predforte , allergan , irvine , ca , usa ) was commenced in tapering doses ( starting dose of 4 times / day ) .
primary outcome measure was a response to therapy which was clinically assessed by comparing the size of infiltrate at trial entry and after 2 weeks of systemic and topical antiviral treatment .
secondary outcome measure was improvement in best - corrected visual acuity from baseline to end of 10 weeks .
any surgical intervention or adverse incident occurring during the course of therapy was recorded to assess safety of the treatment .
treatment failure was considered in cases where there was an increase in the area of infiltrate , appearance of fresh infiltrate , < 10% decrease in the stromal keratitis or corneal perforations requiring keratoplasty within first 2 weeks .
cyanoacrylate tissue adhesive application for management of extreme thinning was noted as a surgical intervention .
however , these patients continued to remain in the study and response to therapy was recorded .
the mean age of the patient was 51.53 years ( range : 30 - 80 years ) .
ten patients showed predilection for the left eye ( 72.92% ) and three patients for the right eye ( 23.08% ) .
eight patients ( 61.5% ) were classified as early presentation and five patients ( 38.5% ) as late presentation .
dna pcr was done for all cases out of which 11 were positive ( 74% ) .
the area of infiltration at presentation ranged from 2 to 31 mm with a mean of 8.52 mm ( standard deviation [ sd ] = 8.19 mm ) .
three patients ( 23.08% ) had up to one - third thinning of the corneal stroma and five patients ( 38.46% ) had thinning up to two - third corneal stroma and rest five ( 38.46% ) had severe thinning more than two - third corneal stroma .
after 2 weeks of antiviral therapy , the area of infiltration ranged from 1 to 16 mm , with a mean of 5.12 mm ( sd = 4.62 mm ) .
area of infiltration at trial entry and at the end of 2 weeks of antiviral treatment was statistically significant ( p = 0.007 ) .
ten patients ( 76.9% ) showed complete resolution of the epithelial defect at 2 weeks . figs .
( b ) patient on therapy at the end of 2 weeks ( 5 mm ) .
( c ) image showing complete resolution at 10 weeks ( a ) patient at presentation ( 31 mm ) .
( c ) image showing complete resolution at 10 weeks ( a ) patient at presentation ( 19.5 mm ) .
( c ) image showing complete resolution at 10 weeks three eyes ( 23.08% ) developed spontaneous perforation within the first 2 weeks .
all three had prolonged the duration of presentation ( more than 6 weeks ) , more than two - third corneal thinning and more than 8.1 mm area of infiltration .
these patients responded well to antiviral therapy after application of tissue adhesive . on removal of tissue adhesive at 6 weeks
visual acuity ( logmar ) at presentation ranged from 2.20 to 0.48 with a mean of 1.75 ( sd = 0.508 ) . at the end of 2 weeks
, visual acuity ranged from 0.78 to 2.20 logmar with a mean of 1.44 ( sd = 0.41 ) . at the end of 10 weeks
, visual acuity ranged from 1.40 to 0.48 with a mean of 1.087 ( sd = 0.387 ) .
the improvement in visual acuity from presentation up to 2 weeks was not statistically significant ( p = 0.06 ) ; however , it was statistically significant at the end of 10 weeks ( p = 0.003 ) .
after initiation of topical steroid therapy at the end of 2 weeks , all patients showed symptomatic improvement .
no patient deteriorated after initiation of topical steroid therapy . at the end of 10 weeks
, all patients presented with a vascularized corneal scar indicating the complete resolution of keratitis and response to therapy .
this study shows that topical and systemic acyclovir for treatment of nsk facilitated healing of ulceration .
nsk , in contrast to immune - mediated stromal keratitis and stromal edema due to hsv endotheliitis is essentially an infective disease with a demonstration of live virus in the corneal stroma .
this study confirmed the presence of live virus in this disease entity with 74% of the samples showing hsv1 dna in pcr in corneal scraping .
the rationale to use systemic acyclovir for treatment of nsk was based on evidence in the literature that therapeutic concentrations of the drug are present in the plasma following oral administration .
the heds study also showed a beneficial response to systemic acyclovir in treatment of herpetic uveitis , another condition where the live virus has been demonstrated .
this study demonstrated that systemic acyclovir in addition to topical antiviral therapy is effective in treatment of nsk .
there was a significant resolution of stromal infiltration within 2 weeks of initiation of therapy .
however , steroids have a beneficial role in reducing the overall inflammation , discomfort , and pain of the patient .
this has also been seen in this study where after initiation of topical steroids all patients showed symptomatic improvement during the course of the trial .
corneal clarity improved with steroids resulting in an improvement in visual acuity . in our study , the average onset of symptoms to diagnosis was 2.5 weeks and 8 out of 13 patients were being treated as suppurative keratitis .
all three patients presented late , and with more than two - third stromal thinning at enrollment of study .
the regime of systemic and topical acyclovir therapy was not effective in halting the progression to perforation , in cases with extreme thinning .
all patients underwent cyanoacrylate tissue adhesive for tectonic support in this group , while systemic acyclovir facilitated eradication of infection .
signicant improvement of visual acuity was noted in the majority of cases in this study .
however , this improvement was significant at the end of 10 weeks , during this period , topical steroid drops were also given .
low - dose topical steroid therapy did not have any side effects in our study .
it is unclear from this study whether only antiviral therapy alone would have resulted in similar outcomes .
this study shows a beneficial effect of combination therapy of topical and systemic acyclovir in the treatment of nsk .
a randomized , controlled trial is required to determine the beneficial effect of topical acyclovir and oral acyclovir alone .
nsk is an uncommon but distinct clinical entity in the varied presentations of ocular hsv .
the disease can have extended periods of morbidity and if left untreated can have a poor visual outcome .
 purpose : to evaluate the efficacy of systemic and topical antiviral therapy in the treatment of active herpes simplex virus ( hsv ) necrotizing stromal keratitis ( nsk).design : prospective interventional case series.methodology:patients with a diagnosis of hsv nsk based on history and clinical findings were enrolled in the study . 
 a standard protocol was used for microbiologic investigations . 
 ten weeks regime of systemic acyclovir and 2 weeks of topical acyclovir was given . 
 complete ophthalmic examination was performed at every visit . 
 outcome measures were a reduction in the area of infiltration and improvement in visual acuity.results:fifteen patients were enrolled in the study . 
 the mean age of presentation was 51.53 years . 
 the duration of symptoms at presentation ranged from 2 to 8 weeks . 
 hsv1 
 dna polymerase chain reaction was positive in 70% cases of those tested . 
 area of infiltration at trial entry and at the end of 2 weeks of antiviral treatment reduced significantly ( p = 0.007 ) . 
 all patients showed a complete resolution of keratitis at the end of study.conclusion:topical and systemic acyclovir for treatment of nsk facilitates healing of ulceration . 
 topical steroids after initial antiviral therapy are safe and decreases inflammation and improve visual recovery . 
 early initiation of therapy has better outcomes as compared to late presentations . 
Methodology
Study design
Study protocol
Results
Discussion
Conclusion
Financial support and sponsorship
Conflicts of interest