Up to September 2019, there were 95 cases of culture positive NTM endophthalmitis reported in the literature apart from three cases of this current study [1, 5-7, 13-54]. Demographic data of all 98 cases were shown in table 1. There were additional 33 case reports and 14 case series (Appendices 1 and 2). There were 7 duplicated cases. The age ranged from 13 to 89 years with mean age of 61.1±18.7 years. There were 46 males (46.9%), 49 females (50%), and the data were unavailable in three cases. The common symptoms were pain, decreased vision and redness. The clinical signs are conjunctival injection, hypopyon, anterior chamber inflammation, granulomatous keratic precipitates, vitreous inflammation, and paradoxical deterioration after steroid therapy [3, 4, 35]. Of total, exogenous endophthalmitis and endogenous endophthalmitis occurred in 85 cases (86.7%) and 13 cases (13.3%), respectively.
In exogenous endophthalmitis cases, the mean age was 64.1±17.4 years (range 13-89 years) and 39 patients (47.6%) were male. Endogenous endophthalmitis patients had the mean age of 42.7±16.2 years (range 17-67 years) and 7 (53.8%) were male.
Table 1 Demographic information of patients with Non-tuberculous mycobacterium endophthalmitis
|
|
Exogenous
(n=85)
|
Endogenous
(n=13)
|
Total
(n=98)
|
Sex
|
|
|
|
Male
|
39 (45.9)
|
7 (53.8)
|
46 (46.9)
|
Female
|
43 (50.6)
|
6 (46.2)
|
49 (50.0)
|
Mean age in years (SD)
|
64.1 (17.4)
|
42.7 (16.2)
|
61.1 (18.7)
|
Systemic disease
|
|
|
|
None
|
24 (28.2)
|
1 (7.7)
|
25 (25.5)
|
Human Immunodeficiency Virus infection
|
0
|
4 (30.8)
|
4 (4.1)
|
Under immunosuppressants
|
9 (10.6)
|
4 (30.8)
|
13 (13.3)
|
Diabetes mellitus
|
7 (8.2)
|
2 (15.4)
|
9 (9.2)
|
Post-organ transplantation
|
1 (1.2)
|
2 (15.4)
|
3 (3.1)
|
Immunological diseases
|
5 (5.9)
|
1 (7.7)
|
6 (6.1)
|
Cancers
|
4 (4.7)
|
1 (7.7)
|
5 (5.1)
|
Previous mycobacterial tuberculosis
|
2 (2.4)
|
2 (15.4)
|
4 (4.1)
|
SD; Standard Deviation
Exogeneous endophthalmitis occurred in 53 patients underwent cataract surgery (62.4%). Other causes of exogenous endophthalmitis included post-glaucoma drainage implant (12 cases, 14.1%), post-corneal transplantation (6 cases, 7.1%), post-intravitreal injection (2 cases, 2.4%), post-scleral buckling exposure (2 cases, 2.4%), post-vitrectomy in (2 cases, 2.4%), ocular trauma (2 cases, 2.4%), corneal ulcer (2 cases, 2.4%), post-keratoprosthesis (1 case, 1.2%), post-trabeculectomy (1 case, 1.2%), and post-laser-assisted in situ keratomileusis (LASIK) (1 case, 1.2%). The presentation started from 1 day to 60 months with a median interval of 1 month after the surgery. From available information on systemic immunological conditions, 16 (18.8%) of exogenous endophthalmitis patients were immunocompromised.
Of 13 endogenous endophthalmitis patients, 4 (30.8%) were HIV infected and 2 (15.4%) had diabetes mellitus. Four of them (30.8%) received immunosuppressive agents due to autoimmune disease, organ transplantations, or cancers. Only one case (7.7%) was a healthy host. Among endogenous endophthalmitis cases, 4 (30.8%) had a clear evidence of disseminated NTM infection prior to intraocular infection. Others had neither unmentioned systemic infection nor unavailable information. The median duration between the onset of systemic infection and ocular presentation was 3 months which ranged from 15 days to 8 months. (Table 2) From all endophthalmitis cases, there were 4 patients (4.1%) with previous mycobacterial tuberculosis infection. There were one with a lymph node tuberculosis and one with pulmonary tuberculosis (case 1), which had been completely treated 2 years ago. The other two cases had recent ocular (case 2) and disseminated tuberculosis which were undergoing antimycobacterial treatment.
Table 2 Primary source of infection of Non-tuberculous mycobacterium endophthalmitis
|
|
Exogenous
(n=85)
|
Endogenous
(n=13)
|
Systemic infections
|
|
|
|
|
|
|
|
|
Disseminated NTM infection
|
-
|
4 (30.8%)
|
Unknown source
|
-
|
6 (46.2%)
|
Not mentioned
|
-
|
3 (23.1%)
|
Ocular diseases or injuries
|
|
|
Cataract surgery
|
53 (62.4)
|
-
|
Glaucoma drainage device
|
12 (14.1)
|
-
|
Corneal transplantation
|
6 (7.1)
|
-
|
Corneal ulcer
|
2 (2.4)
|
-
|
Intravitreous injection
|
2 (2.4)
|
-
|
Scleral buckling
|
2 (2.4)
|
-
|
Trauma
|
2 (2.4)
|
-
|
Vitrectomy
|
2 (2.4)
|
-
|
Keratoprosthesis
|
1 (1.2)
|
-
|
Laser-assisted in situ keratomileusis (LASIK)
|
1 (1.2)
|
-
|
Trabeculectomy
|
1 (1.2)
|
-
|
Not mentioned
|
1 (1.2)
|
-
|
From our reviewed data, positive cultures were found in vitreous (38/98, 38.8%), aqueous (56/98, 57.1%), corneal tissue (8/98, 8.2%), or eviscerated tissue (4/98, 4.1%). In cases of post-operative endophthalmitis, NTM was also found in the removed intraocular devices (6/85, 7.1%). The duration between the onsets of ocular infection to final diagnosis varied from 3 days to 12 months with a median of 18 days. The causative organism in exogenous endophthalmitis was mainly identified as rapid growers; M. chelonae-abscessus group in 65 patients (76.5%), M. fortuitum in 10 patients (11.8%), M. manitobense in 2 patients (2.4%), and M. goodii in 1 patient (1.2%). The rests were slow growers; M. gordonae in 1 patient (1.2%), M. haemophilum in 1 patient (1.2%), and M. terrae in 1 patient (1.2%). On the other hand, the majority of pathogen in endogenous endophthalmitis was slow growers; M. avium in 4 patients (30.8%), M. kansasii in 1 patient (7.7%), M. haemophilum in 1 patient (7.7%), and M. triplex in 1 patient (7.7%). There was 1 patient (7.7%) with mixed infection of M. fortuitum and M. bovis. The only rapid grower, M. chelonae, was identified in 1 patient (7.7%). (Table 3)
Table 3 Non-tuberculous mycobacterium species identified in endophthalmitis
|
|
Exogenous
(n=85)
|
Endogenous
(n=13)
|
Rapid growers
|
|
|
M. chelonae/abscessus group
|
65 (76.5)
|
1 (7.7)
|
M. fortuitum
|
10 (11.8)
|
0
|
M. goodie
|
1 (1.2)
|
0
|
M. manitobense
|
2 (2.4)
|
0
|
Slow growers
|
|
|
M. avium
|
0
|
4 (30.8)
|
M. kansasii
|
0
|
1 (7.7)
|
M. triplex
|
0
|
1 (7.7)
|
M. haemophilum
|
1 (1.2)
|
1 (7.7)
|
M. gordonae
|
1 (1.2)
|
0
|
M. terrae
|
1 (1.2)
|
0
|
Mixed infection
|
|
|
M. fortuitum and M. bovis
|
0
|
1 (7.7)
|
Unspecified species
|
4 (4.7)
|
4 (30.8)
|
The treatment information was retrieved from 75 exogenous and 8 endogenous endophthalmitis patients. In exogenous endophthalmitis, systemic treatment was given in 51 patients (68.0%) including macrolides (40 patients), aminoglycosides (19 patients), fluoroquinolones (13 patients), cephalosporins (8 patients), beta-lactams (3 patients), vancomycin (3 patients), and clindamycin (1 patient). Local antibiotics (subconjunctival, intracameral, or intravitreal injection) were administered in 65 cases (86.7%) including aminoglycosides (56 patients), vancomycin (49 patients), cephalosporins (31 patients), fluoroquinolones (2 patients), and beta-lactams (1 patients). The final regimens were mainly macrolides, fluoroquinolones and aminoglycosides with a duration ranged from 1 week to 12 months.
Of 8 endogenous endophthalmitis patients, systemic treatment was administered in 6 patients (75.0%) included macrolides (4 patients), fluoroquinolones (4 patients), beta-lactams (2 patients), and aminoglycosides (1 patients). Local antibiotics were given in 4 cases (50.0%). All of them received aminoglycosides. Cephalosporins were used in 1 patient. The final regimen was either macrolides or fluoroquinolones with a duration ranged from 3 weeks to 9 months.
Additional surgeries were performed to get rid of infection in several cases. PPV was done in 52 exogenous endophthalmitis patients (61.2%) and 4 endogenous endophthalmitis patients (30.8%). Enucleation was performed in 17 exogenous endophthalmitis patients (20.0%) and 3 endogenous endophthalmitis patients (23.1%). In exogenous endophthalmitis cases, 39 of them (45.9%) underwent implant removal. (Table 4)
Table 4 Treatment summary of Non-tuberculous mycobacterium endophthalmitis
|
|
Exogenous
n (%)
|
Endogenous
n (%)
|
Medical treatments
|
|
|
Systemic
|
51 (68.0)
|
6 (75.0)
|
Local*
|
65 (86.7)
|
4 (50.0)
|
Surgical treatments
|
|
|
Pars plana vitrectomy
|
52 (61.2)
|
4 (30.8)
|
Enucleation, evisceration
|
17 (20.0)
|
3 (23.1)
|
Device removal
|
39 (45.9)
|
-
|
*Local antibiotics; intravitreous, subconjunctival, and intracameral injection
In exogenous endophthalmitis, the initial BCVA were better than 6/60 in 20 patients (29.9%) and worse than 6/60 in 47 patients (70.1%). The final BCVA were better than 6/60 in 21 patients (25.6%) and worse than 6/60 in 61 patients (74.4%). Complications occurred in 30 patients (30.6%); hypotony or phthisis in 18 patients (21.2%), retinal detachment in 5 patients (5.9%), secondary glaucoma in 3 patients (3.5%), corneal perforation in 3 patients (3.5%), and optic atrophy in 2 patients (2.4%).
In endogenous endophthalmitis, there were 2 patients (33.3%) with BCVA better than 6/60 and 4 patients (66.7%) with BCVA worse than 6/60 at the beginning. At the final visit, 1 patient (11.1%) gained BCVA better than 6/60 and 8 patients (88.9%) had BCVA worse than 6/60. Complications occurred in 5 patients (38.5%); hypotony or phthisis in 3 patients (23.1%), retinal detachment in 1 patient (7.7%), secondary glaucoma in 1 patient (7.7%), and corneal perforation in 1 patient (7.7%). There were no significant differences of initial and final BCVA between both types of NTM endophthalmitis (p=1.000, 0.446, respectively). (Table 5)
Table 5 Clinical outcome of Non-tuberculous mycobacterium endophthalmitis
|
|
Exogenous
n (%)
|
Endogenous
n (%)
|
|
Initial best-corrected visual acuity
|
|
|
|
6/6-6/60
|
20 (29.9)
|
2 (33.3)
|
|
Worse than 6/60
|
47 (70.1)
|
4 (66.7)
|
|
Final best-corrected visual acuity
|
|
|
|
6/6-6/60
|
21 (25.6)
|
1 (11.1)
|
|
Worse than 6/60
|
61 (74.4)
|
8 (88.9)
|
|
Complications
|
30 (30.6)
|
5 (38.5)
|
|
Hypotony, phthisis
|
18 (21.2)
|
3 (23.1)
|
|
Retinal detachment
|
5 (5.9)
|
1 (7.7)
|
|
Glaucoma
|
3 (3.5)
|
1 (7.7)
|
|
Corneal perforation
|
3 (3.5)
|
1 (7.7)
|
|
Optic atrophy
|
2 (2.4)
|
0
|
|