Since the first reported case of NTM endophthalmitis in 1973, the organism had been increasingly reported because of improved microbiological diagnostic methods and enlarged immunocompromised hosts in recent years [39].
In this review, endophthalmitis caused by NTM equally occurred in both males and females. The age of onset was approximately in the fourth to sixth decades of life. NTM exogenous endophthalmitis could occur after uneventful ocular surgery, even in healthy hosts. The infection often occurred within 1 month after ocular surgery. Cataract surgery was accounted for the most common procedure related to the infection. On the other hand, NTM endogenous endophthalmitis mainly took place in immunocompromised patients especially those with history of mycobacterial systemic infection.
Overall demographic data did not change from previous reviews of ocular NTM infections. In 2015, Kheir et al reported that NTM endophthalmitis had no gender differences and the median age of presentation was 44 years. Among all exogenous endophthalmitis patients, the infection usually occurred after ocular intervention which 48.6% was cataract surgery with an average time of 11.5 weeks after ocular surgery [3]. In 2012, Moorthy et al reported an average period of 1 month after a procedure, while all endogenous endophthalmitis cases were either iatrogenic or acquired immunosuppression [4]. Likewise, Kheir et al reported that more than half (60.0%) of endogenous endophthalmitis cases was associated with immunodeficiency status and previous disseminated mycobacterial infection [3].
The most common causative pathogens of ocular infections are rapidly growing NTMs. M. abscessus, M. chelonae, and M. fortuitum are responsible for the majority of cases [3, 4]. However, in this review, we found that most of exogenous endophthalmitis cases were caused by rapid growers, while slow growing NTMs were leading causes of endogenous endophthalmitis. According to different natures of NTMs, slow growers are generally found in pulmonary and lymph node diseases [55]. Along with immunocompromised state of hosts leading to susceptibility for systemic spreading, this could explain why slow growing NTMs were apparently related with endogenous endophthalmitis in this study.
In addition to the published literature, there were three exogenous endophthalmitis cases reported from our hospital; M. abscessus, M. fortuitum, and M. haemophilum endophthalmitis. All of them were male in fifth to sixth decade similar to previously reported cases. Two rapid growers (M. absecssus and M. fortuitum) were identified early after laser capsulotomy and reparation of exposed tube shunt respectively, while a slow grower NTM, M. haemophilum, was found late in a case with multiple trabeculectomies. Despite the types of organism, the onset of these cases was gradual, and the clinical manifestation was subtle at the beginning mimicking chronic uveitis. Their presentation misled the ophthalmologists resulting in delayed investigation and treatment.
M. abscessus belongs to M. Chelonae/abscessus group. Its identification was relying on identification methods, such as PCR restriction analysis and DNA sequencing [56]. Among the NTMs, M. chelonae-abscessus group was known as having the highest resistant rate to antibiotics and anti-tuberculous drugs due to the formation of biofilm [37, 56].
The onset of M. chelonae/abscessus endophthalmitis varied from immediate to 3 years after operation and the infection generally presented with chronic granulomatous inflammation. In post-cataract surgery, corneal infiltration around the cataract wound and white plaque-like material on the intraocular lens implant had been observed [5]. The same pattern was observed in our patient. In the previous literature, M. chelonae/abscessus group was generally associated with poor visual outcomes [5]. Total of 82.3% of cases ended up with visual impairment, evisceration, enucleation, or phthisis. The poor prognosis is due to delay diagnosis and treatment and the organism’s ability to form a biofilm [1, 6, 9]. The diagnosis of our case was made within 6 weeks after capsulotomy which caused acute active inflammation. This presentation led to early vitrectomy resulting in a successful treatment. From literature review, there were only 11 eyes that showed final BCVA of 6/60 or better [7, 20, 29, 31, 38, 40, 42, 46, 51]. Stewart et al reported a case of M. abscessus endophthalmitis with a full visual recovery [49].
M. fortuitum endophthalmitis was reported in 11 cases previously. The incubation period ranged from 10 days to 20 months [1, 7, 21, 27, 40, 43, 44]. As a rapid growing nature, our patient had the onset of 1 month postoperatively. The progression of disease and the clinical findings were similar to almost all reported cases. At early stage, with surgical repair of exposed shunt, infectious uveitis could not be excluded. However, the treatment of this patient was misled by false positive Quantiferon-TB test and treated partially with standard anti-tuberculosis drugs. The suspicion of NTM infection was made after clinical worsening despite anti-tuberculosis and anti-bacterial treatment, and the organism was identified 3 weeks after aqueous aspiration. Despite the delay in diagnosis, the patient ended with favorable vision. Similarly, from a review, 6 eyes (54.5%) of M. fortuitum endophthalmitis gained final BCVA of 6/60 or better [7, 27, 40, 43].
M. haemophilum endophthalmitis in our patient was previously reported to be the first case of postoperative endophthalmitis in the literature [12]. In 2007, Modi et al reported the first case of disseminated M. haemophilum infection in a patient with immunosuppressive medication after a cardiac transplantation [41, 57, 58]. He had the gradual course of ocular infection with multiple skin nodules before turning into a suppurative endophthalmitis and finally enucleated. Our patient also had similar clinical course which ended up with purulent endophthalmitis and visual loss despite combination of intraocular and systemic antimicrobial treatment.
NTM endophthalmitis has a variable of clinical syndrome which can mimic chronic intraocular inflammation and makes initial confusion with other low virulent bacterial and fungal infection [10]. Misdiagnosis with other organisms has been commonly reported before the final diagnosis [33]. Clinical suspicion of NTM infections is necessary especially in immunocompromised patients, with chronic granulomatous intraocular inflammation and intermittent response with anti-inflammatory drugs. Repeat vitreous and aqueous cultures are required to identify the causative organism in which determines the choice of antibiotics. The treatment of NTM endophthalmitis includes the combination of local and systemic antibiotic therapy with or without surgical removal of the implants. The patient who does not response to medical treatment or has an ocular implant is considered surgical therapeutic interventions [3, 10].
Specific guidelines for antibiotics and duration of treatment are still unestablished. The regimen is based on drug sensitivity information and clinical response. Standard anti-tuberculosis drugs such as isoniazid, rifabutin, rifampin, ethambutol, and streptomycin are commonly prescribed. However, NTM are often resistant to these regimens and alternative antimicrobials have emerging roles for NTMs infection due to the potency, pharmacokinetic property, and safety. Especially among rapidly growing NTM, a combination of aminoglycosides, fluoroquinolones and macrolides has shown successful outcome [3, 8, 10]. On the other hand, slow growers are more sensitive to anti-tuberculosis drugs [4].
There are some mentionable limitations. As NTM endophthalmitis is an uncommon condition, this review was a collection of case reports and case series. Nevertheless, we summarized all available information and demonstrated the characteristics as well as the causative pathogens and the outcomes of NTM endophthalmitis. Lack of required details from the literature review and inaccessibility of non-English data could miss some incomplete information.