Long-Term Outcome of Treatment with 2% Topical Ganciclovir Solution in Cytomegalovirus Anterior Uveitis and Corneal Endotheliitis

Figures & data

Table 1 Patient Demographics

Variable	Overall Enrolled Eyes (N = 38)			Recurrence (N = 17)	Non-Recurrence (N = 21)	p value
	Mean or N	Median	Range	Mean or N	Mean or N
Age (years)	55.68 ± 12.43	52	36–83	55.06 ± 12.75	56.19±12.46	0.79^a
Gender						0.70^b
Male	28 (73.7%)			16 (76.2%)	12 (70.6%)
Female	10 (26.3%)			5 (23.8%)	5 (29.4%)
Medical history
Diabetes mellitus	4			1	3
Hypertension	7			4	3
Coronary artery disease	2			1	1
Asthma	2			0	2
Follow-up duration (month)	45.68 ± 28.47	41	12–105	54.65 ± 27.87	38.43 ± 27.47	0.056^c
Diagnosis
Uveitis	34 (89.5%)			16 (94.1%)	18 (85.7%)	0.40^b
Endotheliitis	4 (10.5%)			1 (5.9%)	3 (14.3%)

Notes: ^aIndependent t-test, age difference between recurrence and non-recurrence group. ^bDouble tailed Chi-square test, gender and diagnosis difference between recurrence and non-recurrence group. ^cMann-Whitney U-test, follow-up duration difference between recurrence and non-recurrence.

Table 2 Treatment Outcomes: Comparison of Primary and Secondary Outcome Parameters in Initial Treatment and Last Follow-Up

Variable	Initial Treatment (N = 38)			Last Follow-Up (N = 38)			p value
	Mean or N	Median	Range	Mean or N	Median	Range
Response (Yes/No)
Yes				37
No				1
Recurrence number				21
Recurrence (relapse/year)				0.13
Clinical findings
CDVA (LogMAR)	0.41 ± 0.27	0.4	0–1.1	0.27 ± 0.30	0.25	0–2	0.023^a
Cell (+)	1.14 ± 0.73	1	0–2	0.30 ± 0.53	0	0–1	0.001^b, c
Keratic precipitates							0.001*^b
Present	32 (84.2%)			15 (39.5%)
Absent	6 (15.8%)			23 (60.5%)
IOP (mmHg)	26.47 ± 11.86	23	12–60	14.49 ± 3.00	15	7–19	<0.001*^a
Treatment
2% ganciclovir	38 (100%)			38 (100%)
Topical steroid	33 (86.8%)			25 (73.7%)			0.039^b
Topical glaucoma therapy							0.075^a
No treatment	6 (15.8%)			9 (23.7%)
Monotherapy	16 (42.1%)			18 (47.4%)
Dual therapy	8 (21.1%)			10 (26.3%)
Tritherapy	8 (21.1%)			1 (2.6%)
Oral acetazolamide	10 (26.3%)			0 (0%)			<0.001*^b
IV mannitol	6 (18.8%)			0 (0%)			<0.001^b

Notes: ^aDouble-tailed paired t-test, treatment efficacy, difference between paired initial and last follow-up in continuous parameters. ^bMcnemar’s test, difference between paired initial and last follow-up in categorical parameters (binomial distribution used). ^cCell was measured with Mcnemar’s test by divided into 2 groups (0–0.5+ as less inflammation group and 1+-2+ as more inflammation group). *Statistical significance.

Abbreviations: CDVA, corrected distance visual acuity; IOP, intraocular pressure.

Table 3 Recurrence Analysis: Comparison of Initial Findings in Recurrence and Non-Recurrence Group

Variable	Recurrence (N = 17)			Non-Recurrence (N = 21)			p value
	Mean or N	Median	Range	Mean or N	Median	Range
Initial findings
CDVA (LogMAR)	0.33 ± 0.22	0.30	0.5–0.7	0.51 ± 0.30	0.52	0–1.1	0.061^a
Cell (+)	1.17 ± 0.80	1	0–2	1.11 ± 0.70	1	0–2	0.803^b, c
Keratic precipitates							0.036*^b
Present	16 (94.1%)			16 (76.2%)
Absent	1 (5.9%)			5 (23.8%)
IOP (mmHg)	34.93 ± 12.89	35	12–60	20.55 ± 6.40	20.5	13–33	0.001*^a
Initial treatment
2% ganciclovir	17 (100%)			21 (100%)
Topical steroid	14 (82.4%)			19 (90.9%)			0.461^b
Topical glaucoma therapy							0.208^b
No treatment	2 (11.8%)			4 (19.0%)
Monotherapy	5 (29.4%)			11 (52.4%)
Dual therapy	6 (35.3%)			2 (9.5%)
Tritherapy	4 (23.5%)			4 (19.0%)
Oral acetazolamide	8 (47.0%)			1 (4.8%)			0.001^b
IV mannitol	5 (29.4%)			1 (4.8%)			0.624^b

Notes: ^aIndependent t-test. ^bDouble tailed Chi-square test. ^cCell was measured with double tailed Chi-square test by divided into 2 groups (0–0.5+ as less inflammation group and 1+-2+ as more inflammation group). *Statistical significance.

Abbreviations: CDVA, corrected distance visual acuity; IOP, intraocular pressure.

Table 4 Literature Review of Topical 2% Ganciclovir Solution in Patients with CMV Anterior Segment Infection

Reference	Eyes	Initial Therapy	Maintenance Therapy	Treatment Duration (weeks)	Follow-Up Duration (Months)	Study Design
Keorochana, 2017^Citation21	11	Q2H	Nil	-	12	Efficacy and safety of 2% ganciclovir solution evaluated monthly over a 12-month follow-up period
Su, 2013^Citation10	7	Q2-3H	Q4H	Throughout follow-up	17.29±2.12	Clinical and immunological characteristics in 7 penetrating keratoplasty cases after topical 2% ganciclovir applied
Su, 2014^Citation17	68	Q2-3H	Q4H	Throughout follow-up	39.79±14.96	Comparison of therapeutic outcome of 126 Posner-Schlossman syndrome patients with CMV-positive (68 eyes) and CMV-negative (58 eyes)
Sheng, 2021^Citation9	36	QID	TID-QID	5.13 ± 3.66	36	Prognosis of 98 eyes with Posner-Schlossman syndrome and therapeutic outcomes of 36 CMV-positive eyes proven by IgG ratio of aqueous humor and serum samples
Sheng, 2022^Citation15	46	QID	QID	6.50 ± 4.67	1.5	Comparison of the 2% ganciclovir efficacy in the treatment of Posner-Schlossman syndrome relapses with and without CMV intraocular reactivation by IgG ratio of aqueous humor and serum samples

Abbreviation: CMV, cytomegalovirus.

Table 5 Literature Review of Other CMV Treatment Modalities and Outcomes

Studies	Eyes/Treatment Episodes	Initial Therapy	Maintenance Therapy	Treatment Duration (m)	Follow-Up Duration (m)	Results
Sira and Murray, 2007^Citation24	1	Oral VCV 1 g twice daily	-	11	11	No recurrence
Van Boxtel, 2007^Citation3	5	Oral valGCV 900 mg twice daily for 3 weeks	Oral valGCV 900 mg once daily	8.0±3.6	94.8±87.6	Uveitis quiescent within a few weeks, 1 recurred after cessation of antiviral therapy
Sobolewska, 2014^Citation27	11	Oral valGCV 900 mg twice daily for 3 weeksTopical 0.15% GCV gel 5 times daily	Oral valGCV 450 mg twice daily	20.5±10.1	-	7/11 (63.6%) responsive, 2 recurrences after cessation of antiviral therapy
Harada, 2018^Citation29	17	Oral valGCV 900 mg twice daily for 3 weeks Topical 1% GCV solution 6 times daily	Oral valGCV 450 mg twice daily	6.1±5.5	36.7±22.9	All patients (100%) responsive, 6/12 (50%) recurred during tapering or termination of anti-CMV therapy
Markomichelakis, 2002^Citation26	2	Oral GCV 1000 mg three times daily	-	18±8.5	-	Asymptomatic under antiviral therapy
Chung and Chua, 2005^Citation28	1	Intravitreal GCV	-	-	-	Uveitis quiescent and CMV DNA copies reduced after 2 weeks
Chee, 2010^Citation13	19	Intravenous GCV 5 mg/kg twice daily, oral GCV 1g 3 times daily or oral 900 mg valGCV twice daily for 6 weeks	450 mg twice daily for 6 weeks	3	4.9–54.8	17/19 response, 14/17 recurred
	4	GCV implant: 4.5 mg GCV	-	-	-	4/4 response, 4/4 recur
	7	Intravitreal GCV 2 mg/0.1ml weekly	-	3	-	4/7 response, 4/4 recur
	17	Topical 0.15% GCV gel 4 times daily	-	3	-	11/17 response, 5/11 recur
De Schryver, 2006^Citation25	5	Intravenous GCV or foscarnet at least 2 weeks	Oral valGCV 450 mg twice daily for 2 months	2.5	14.8±6.9	2 patients recurred after cessation of therapy
	1	Oral valGCV 450 mg twice daily for 2 months	-	2	24	Recurrence after cessation of therapy
Koizumi, 2017^Citation12	7	Topical 0.15% GCV gel 6 times daily	-	3	3	Inflammation controlled and no clinical recurrence at 12-week administration
Pavan-Langston, 2012^Citation14	1	Topical 0.15% GCV gel every 2 hours	Topical 0.15% GCV gel twice daily	4.5	≥24	Rapid resolution of uveitis but relapse after discontinuation
Fan, 2016^Citation22	10	Topical 0.5% GCV every 2 hours	Topical 0.5% GCV four times daily	Throughout follow-up	48.1±25.1	All responsive with clear graft or cornea, 1 had recurrence once

Abbreviations: CMV, cytomegalovirus; GCV, ganciclovir; VCV, valcyclovir; valGCV, valganciclovir.

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