Epidemiology, risk factors, and clinical outcomes in severe microbial keratitis in South India

Figures & data

Table 1. Socio-demographic and clinical risk factors associated with bacterial, fungal, and Acanthamoeba keratitis at presentation.

Risk factor	All microbial keratitis	Bacterial keratitis	Fungal keratitis	Acanthamoeba keratitis	No organism	p-Value*
	N = 252	N = 19	N = 191	N = 18	N = 20
Socio-demographic
Age, years (median, IQR)	50 (37–60)	60 (35–65)	50 (36–58)	39 (34–55)	53 (43–61)	0.066
Gender (% male)	162 (64)	12 (63)	123 (64)	11 (61)	13 (65)	0.993
Occupation: no. agricultural workers (%)	159/251 (63)	15 (79)	121 (64)	11 (61)	10 (50)	0.311
Had primary education or greater (%)	135/246 (55)	8 (42)	107/186 (57)	9/17 (53)	10 (50)	0.577
Current tobacco use (%)	34/234 (14)	4/16 (25)	23/178 (13)	1 (6)	6/18 (33)	0.047
History
Symptom duration before presentation to AEH, days (median, range)	7 (5–15)	9 (5–15)	7 (4–11)	30 (20–60)	10 (7–21)	<0.001
Symptom duration before presentation to any healthcare provider (HCP), days (median, range)	2 (0–3)	2 (0.5–5)	2 (0–3)	2 (0–7)	0 (0–3)	0.547
History of eye trauma (%)	181 (72)	13 (68)	134 (70)	13 (72)	17 (85)	0.563
Trauma with vegetative matter (%)	82/251 (33)	10/13 (77)	56/133 (42)	3/13 (23)	9/17 (53)	0.033
Prior antifungal use (%)	125/220 (57)	7/16 (44)	98/169 (58)	10 (59)	8/15 (53)	0.727
Prior antibiotic use	162/220 (74%)	11/16 (69%)	123/169 (73%)	14/17 (82%)	11/15 (71%)	0.825
Prior steroid use (%)	25/220 (11)	1/16 (6)	16/169 (9)	7/17 (41)	1/15 (7)	0.001
Traditional medicine use (%)	48 (19)	4 (21)	37 (19)	5 (28)	2 (10)	0.578
Plant-based traditional medicine used (%)	21/47 (45)	2/4 (50)	15/36 (42)	3/5 (60)	1/2 (50)	0.879
Prior MK in affected eye (%)	9 (4)	1 (5)	8 (4)	0 (0)	0 (0)	0.627
Diabetes mellitus (%)	17 (7)	0 (0)	15 (8)	0 (0)	1 (5)	0.356
Initial clinical features
Stromal infiltrate size, mm^2 (median, IQR)	4.5 (3.5–5.9)	3.9 (3.2–6.1)	4.5 (3.3–5.5)	6.8 (5.3–8.0)	5.2 (4.0–6.1)	<0.001
Posterior 1/3 of cornea affected at presentation (%)	168/251 (67)	14 (74)	123 (64)	12 (71)	17 (85)	0.261
Entropion, Ectropion, or lagophthalmos present (%)	12 (5)	2 (10)	8 (4)	0 (0)	2 (10)	0.310
Blocked tear duct (%)	19 (7)	4 (21)	12 (6)	0 (0)	3 (15)	0.039

*Bacterial, fungal, and Acanthamoeba groups compared for statistically significant differences using chi-square test (for proportions) or Kruskal–Wallis test (non-parametrically distributed variables).

Table 2. Proportion of study participants with mild, moderate, or severe visual impairment (VI) or blindness in affected eye at presentation and at final visit, as per the World Health Organization criteria.

Risk factor	Totals (%)	Bacterial keratitis (BK) (%)	Fungal keratitis (FK) (%)	Acanthamoeba keratitis (AK) (%)	No organism (%)	p-Value*
Visual acuity (Snellen VA) at presentation	N = 244	N = 19	N = 189	N = 16	N = 20
Normal (<6/9)	22 (9)	1 (5)	19 (10)	1 (6)	1 (5)	0.773
Mild VI (6/9 to 6/18)	24 (10)	1 (5)	21 (11)	0 (0)	2 (10)	0.468
Moderate VI (>6/18 to 6/60)	35 (14)	2 (10)	31 (16)	1 (6)	1 (5)	0.369
Severe VI (>6/60 to 3/60)	139 (57)	13 (68)	102 (54)	11 (69)	13 (65)	0.370
Blind (>3/60)	24 (10)	2 (10)	16 (8)	3 (19)	3 (15)	0.485
VA at final visit	N = 221	N = 18	N = 185	-	N = 18
Normal	32 (14)	0 (0)	30 (16)		2 (11)	0.155
Mild VI	43 (19)	3 (17)	36 (19)	-	4 (22)	0.915
Moderate VI	34 (15)	2 (11)	28 (15)	-	4 (22)	0.641
Severe VI	76 (34)	7 (39)	65 (35)	-	4 (22)	0.489
Blind	36 (16)	6 (33)	26 (14)	-	4 (22)	0.413

*Proportion of BK, FK, and AK groups within each visual acuity category compared with all others for statistically significant differences using chi-square test.

Table 3. Clinical features in bacterial, fungal, and Acanthamoeba keratitis at presentation.

Ulcer appearance	Bacterial keratitis, BK (n = 19) (%)	Fungal keratitis, FK (n = 191) (%)	Acanthamoeba keratitis, AK (n = 18) (%)	p-Value*
Feathery margin	5 (26)	134 (70)	2 (11)	<0.001
Raised profile	3 (16)	48 (25)	0 (0)	0.039
Dry texture of slough	1 (5)	77 (40)	5 (28)	0.007
Satellite lesions	5 (26)	70 (37)	2 (11)	0.070
Non-yellow infiltrate	12 (63)	141 (74)	16 (89)	0.197
Pigmented ulcer	0 (0)	9 (5)	0 (0)	0.404
Ring infiltrate	8 (42)	54 (28)	16 (89)	<0.001
Perineural infiltrate	0 (0)	1 (0.5)	1 (6)	0.083
Corneal neovascularization	5 (26)	22 (11)	3 (17)	0.172
DM folds	6 (32)	94 (49)	6 (33)	0.172
Endothelial plaque	10 (53)	75 (39)	4 (22)	0.164
Hypopyon	17 (89)	120 (63)	6 (33)	0.002
Cells and/or flare in AC	11/12 (92)	102/148 (69)	6/12 (50)	0.085
Keratic precipitates	6 (32)	55/183 (30)	4/16 (25)	0.900

*Comparison of all three groups (BK, FK, and AK) to assess for statistically significant differences using chi square test.

Table 4. Risk factors associated with clinical outcomes in severe microbial keratitis (*groups compared with chi-square test for proportions and Kruskal–Wallis for continuous non-parametrically distributed variables).

Outcome risk factor	Worse (n = 117)	Good (n = 110)	p-Value*
Socio-demographic
Age, years (median, IQR)	53 (40–60)	45 (35–57)	0.036
Gender (no. male, %)	68 (58)	79 (71)	0.031
Occupation: agricultural (%)	82 (70)	62/109 (57)	0.039
Primary education or more (%)	53 (46)	69 (65)	0.004
Current smoker/tobacco use (%)	14 (13)	18 (17)	0.392
History
Symptom duration, days (median, range)	9 (5–15)	7 (4–10)	<0.001
Any eye trauma (%)	84 (72)	80 (73)	0.875
Trauma with vegetative matter (%)	44 (38)	32/109 (29)	0.190
Prior antifungal use (%)	61/102 (60)	50/94 (53)	0.351
Prior antibiotic use (%)	77 (75)	64 (68)	0.249
Prior steroid use (%)	9 (9)	8 (8)	0.938
Traditional medicine use (%)	20 (17)	22 (20)	0.573
Plant based (%)	7/19 (37)	10/22 (45)	0.577
Seen by another healthcare provider first (%)	103 (88)	98 (89)	0.803
Prior microbial keratitis (%)	6 (5)	3 (3)	0.354
Diabetes mellitus (%)	12 (10)	4 (4)	0.051
Clinical features at presentation
Best-corrected visual acuity-affected eye (median logMAR, IQR)	1.8 (1.7–1.8)	1.7 (0.46–1.8)	<0.001
Stromal infiltrate size, mm^2 (median, IQR)	5.2 (4.0–6.5)	3.8 (3.1–4.7)	<0.001
Posterior 1/3 of cornea involved (N, %)	94 (80)	58 (53)	<0.001
Presence of hypopyon (%)	86 (74)	61 (55)	0.004
Organism
Bacteria (excluding mixed BK/FK) (%)	10 (9)	8 (7)	0.695
Streptococcus pneumoniae (%)	7 (7)	2 (2)	0.108
Fungi (excluding mixed BK/FK) (%)	95 (86)	91 (84)	0.661
Fusarium spp. (%)	28 (24)	46 (42)	0.004
Aspergillus spp. (%)	22 (19)	8 (7)	0.010

Table 5. Univariate and multivariate logistic regression analyses of risk factors associated with worse outcome in severe microbial keratitis (*adjusted for age and gender).

Risk factor	Univariable OR* (95% CI)	p-Value	Multivariable OR (95% CI)	p-Value
Age	1.09 (1.00–1.04)	0.048	0.99 (0.97–1.01)	0.539
Female gender	1.84 (1.05–3.20)	0.032	2.04 (1.03–4.04)	0.040
Presenting ulcer infiltrate size (mm^2)	1.80 (1.45–2.23)	<0.001	1.63 (1.30–2.05)	<0.001
Aspergillus sp. isolated	2.87 (1.19–6.88)	0.018	3.23 (1.26–8.25)	0.014
Posterior corneal involvement	3.33 (1.82–6.11)	<0.001	2.31 (1.16–4.59)	0.017
No formal education	1.68 (0.92–3.05)	0.089	2.30 (1.14–4.62)	0.019
Symptom duration (days)	1.07 (1.03–1.12)	0.001	1.05 (1.00–1.10)	0.032
Vegetative trauma	1.68 (0.94–3.02)	0.079	-	-

Table 6. Organisms identified by culture, light microscopy, and in vivo confocal microscopy by clinical outcome.

Organisms	Perforated or glued (n = 42)	Worse (n = 75)	Improving (n = 70)	Healed (n = 40)
Bacteria (n = 18)	n = 6	n = 4	n = 4	n = 4
Streptococcus pneumoniae	4	2	1	1
Streptococcus viridans	1	0	0	0
Staphylococcus epidermidis	0	1	0	0
Nocardia sp.	0	0	2	1
Pseudomonas aeruginosa	1	1	0	2
Aeromonas sp.	0	0	1	0
Fungi (n = 186)	n = 32	n = 63	n = 59	n = 32
Aspergillus sp.	7	20	7	1
Fusarium sp.	13	15	25	21
Alternaria sp.	0	0	1	0
Bipolaris sp.	0	0	1	0
Curvularia sp.	0	1	2	1
Cylindrocarpon sp.	1	1	0	0
Exserohilum sp.	2	2	0	1
Lasiodiplodia sp.	0	1	1	0
Unidentified hyaline fungi	1	10	4	0
Unidentified dematiaceous fungi	2	3	5	1
Light microscopy positive for fungi, culture negative	5	7	10	5
Light microscopy and culture negative for fungi, but IVCM positive for fungi	1	3	3	2
Mixed bacterial/fungal* (n = 4)	n = 1	n = 2	n = 1	n = 0
Streptococcus pneumoniae	1	0	0	0
Streptococcus viridans	0	1	1	0
Staphylococcus epidermidis	0	1	0	0
Micro/IVCM negative (n = 19)	n = 3	n = 6	n = 6	n = 4
Light microscopy, culture, and IVCM negative for any organism	3	6	6	4

*Mixed infections were culture positive for bacteria (species shown in table) and also positive for fungi detected only in light microscopy and/or in vivo confocal microscopy.