**3. Classification of bacterial endopthalmitis**

condition is known as panophthalmitis. Hence, in endophthalmitis there is involvement of all ocular tissues except the sclera while in panophthalmitis there is involvement of all ocular tissues including the sclera. Panophthalmitis is a devastating fulminant condition associated

Vision loss is mild to moderate with mild pain.

Conjunctival congestion, hypopyon and fibrin deposits are usually not seen. Vitreous opacity

Retinal infiltrates and intra-retinal haemorrhages are very rarely seen.

is usually mild.

**Features Infectious endophthalmitis Non-infectious endophthalmitis**

with hypopyon and fibrin deposits. Also

Treatment Antibiotics and surgery. Topical and/or systemic corticosteroids.

Sterile endophthalmitis is an acute intra-ocular inflammation of the vitreous cavity that resolves without the need of intra-vitreal antibiotics and/or vitreo-retinal surgery. In these cases if vitreous microbiological study is done, it needs to be culture negative. This condition has diverse etiologies and includes systemic auto-immune diseases, local ocular inflammations of unknown cause, endophthalmitis related to lens material and endophthalmitis attributable

Phacoanaphylactic endophthalmitis (lens-induced granulomatous inflammation) is a type of non-infectious endophthalmitis which represents an auto-immune response to lens protein. This is a rare consequence of lens injury which may occur after trauma causing rupturing of the lens capsule, or post surgery such as following extracapsular cataract extraction when residual lens cortex is present. There is a mixed neutrophilic and granulomatous response seen

Phacotoxic endophthalmitis is a condition which was previously used to cover a mixed group of conditions related to cataract surgery and intra-ocular lens implant surgery. However, since inflammation is seen mostly in the anterior segment, the term was changed to toxic anterior segment syndrome (TASS). TASS is caused due to reactions to chemicals (irrigationsolutions, preservatives, drugs, denatured viscoelastics), IOL (intra-ocular lens) materials, instrument sterilization and preparation-related compounds [6,7]. TASS presents with marked decrease in vision and diffuse corneal oedema within 12–24 h of anterior segment surgery, most commonly cataract surgery and, more recently, it has been reported after phakic intra-ocular

vitreous opacity is prominent.

haemorrhages are common.

**Table 1.** Difference between infectious and non-infectious endophthalmitis [4]

Clinical course Rapidly progressive. Slow improvement.

with complete loss of vision and with very poor prognosis [3].

Symptoms Severe vision loss with moderate to severe pain.

22 Advances in Common Eye Infections

Signs Conjunctival congestion is seen along

Slit lamp examination Retinal infiltrates and intra-retinal

**2. Sterile/non-infectious endophthalmitis**

to intra-ocular foreign bodies.

around the lens in histology [5].

lens implantation [6,8].

Endophthalmitis can be categorized as exogenous and endogenous endophthalmitis. Exoge‐ nous endophthalmitis results from direct inoculation as a complication of any intra-ocular surgery (**post-operative endophthalmitis**) and/or blunt or penetrating ocular trauma (**posttraumatic endophthalmitis**). Destruction of intra-ocular tissues may be due to direct invasion by the organism and/or inflammatory mediators of the immune response. **Endogenous endophthalmitis** results from the haematogenous spread of organisms from a distant source of infection [10]. Rarely, keratitis (infection of the cornea), if left untreated, can result in corneal perforation and intra-ocular seeding of organisms leading to endophthalmitis [11]. According to British report, 59% of endophthalmitis were exogenous while 41% were endogenous in origin [12]. In comparison, another study from India suggested that 92.6% were exogenous endophthalmitis and only 7.4% were endogenous endophthalmitis [13]. There are multiple factors responsible for variation in incidence, namely, number of patients included in the study, duration of study, urban versus rural population, pre-disposing factors present, inpatient versus outpatient population and geographical areas of study.

#### **3.1. Post-operative endophthalmitis**

Post-operative endophthalmitis is the most common form of endopthalmitis and it occurs most frequently following cataract surgeries like phacoemulsification and intra-ocular lens implan‐ tation. However, other procedures namely corneal surgeries (penetrating keratoplasty, keratoprosthesis insertion, refractive corneal surgeries), vitreous procedures (intra-vitreal injections, vitrectomies), glaucoma surgical treatments (blebs, glaucoma valve placements), procedures to correct retinal detachment including scleral buckling, and strabismus correction are also associated with varying risks of endophthalmitis. The organisms are generally acquired from eyelid margin and pre-ocular tear film [2,3]. Contributing factors for develop‐ ment of endophthalmitis include dry eye, corneal perforation, systemic immune dysfunction, previous presence of infection like bacterial conjunctivitis, cicatricial disorders (e.g. ocular cicatricial pemphigoid and Steven-Johnson), chronic use of topical antibiotics and both topical and oral corticosteroid use [11]. In various vitrectomies (Pars plana vitrectomy or 25 gauge vitrectomy), diabetes mellitus is recognized as an important risk factor for exogenous en‐ dophthalmitis [14]. Sometimes, cases of clustering of the endophthalmitis are seen, suggesting contaminated materials/solutions or problems with instrument sterilization as responsible [15, 16]. Bacterial infections are the most common cause of post-operative endophthalmitis, and Gram-positive isolates account for the majority of these cases [2]. Coagulase negative *Staphy‐ lococcus* accounts for majority of cases followed by *enterococci* and *streptococci* of viridans group. Among Gram-negative isolates, *Pseudomonas aeruginosa* endophthalmitis is identified [17, 18]. Fungal infections are less common and occur particularly in association with the use of contaminated ocular irrigation fluids [19]. *Candida* spp. (especially *C. parapsilosis*), *Aspergillus* spp. and *Fusarium* spp. are common fungal pathogens responsible for post-operative endoph‐ thalmitis [20]. *E. faecalis* is the causative agent in 4% to 8% of post-operative endophthalmitis cases and is isolated most frequently from infected filtering blebs following glaucoma surgery [10]. The visual outcome is poor and has become a key public health concern because of the emergence of antibiotic resistance to useful antibiotics including vancomycin [21].

Delayed onset infection (> 6 weeks post-operative) may occur due to sequesteration of lowvirulence organisms introduced at the time of surgery or to delayed inoculation of organisms [22, 23]. *S. epidermidis*, *Propionibacterium acnes*, filamentous bacteria (including *Actinomyces* and *Nocardia* sp.), *Hemophilus influenzae*, non-tuberculous mycobacteria (*M. abscessus, M. chelonae* etc.) and *candida* spp. are responsible for chronic or delayed endoph‐ thalmitis [24, 25]. In cases with delayed onset infection, organisms gain access to the eye through either wound abnormalities, suture tracks or filtering blebs. It is more common with glaucoma filtering surgery [26].

#### **3.2. Post-traumatic endophthalmitis**

Penetrating injuries are accompanied by higher infection rate of 1–17% compared to postsurgery cases [10]. The broad prevalence range is due to factors such as frequency of intraocular foreign bodies, distribution of trauma causes, and management strategies. Onset may be acute or delayed, but the most virulent organisms can destroy an eye within hours. Important risk factors for post-traumatic endophthalmitis are the presence of an intra-ocular foreign body (IOFB), the length of time between injury and foreign body removal, delay in closure of the globe, poorer visual acuity at presentation, virulence of organisms and the immune system of the affected individual [27]. Post-traumatic-endophthalmitis-associated isolates are mostly derived from the environment, and hence includes greater variety of organisms than those following ocular surgery. *Staphylococcus* and *Streptococcus* sp. are the most frequent pathogens, followed by *Bacillus cereus and P. aeruginosa* [28]. Filamentous fungi, especially *Aspergillus* sp. and *Fusarium* sp., are also responsible for post-traumatic endoph‐ thalmitis [29]. Bacillus infection is noteworthy as it causes rapid destruction of eye leading to decline in retinal function and vision loss within 24 to 48 h post-infection, despite aggressive treatment and/or surgical intervention. This suggests that even if the infected eye is rendered sterile by antibiotics, ocular damage continues to occur due to the bacterial toxins produced – haemolysins, lipases, enterotoxins and proteases – acting together [30].

#### **3.3. Endogenous endophthalmitis**

Endogenous endophthalmitis is relatively rare accounting for 2% to 8% of all endophthalmitis cases [31]. It results from the introduction of organisms into the eye as a result of haematoge‐ nous spread from a remote primary site of infection [31]. Populations at greatest risk include immunocompromised patients like diabetes, HIV, organ transplant, cardiac disease and malignancy or those on immunosuppressive therapy, patients with prolonged indwelling devices and intra-venous drug abusers [32]. Endogenous endophthalmitis is more common with fungal isolates than with bacterial isolates. Most common fungal pathogens include *Candida* spp*.*, *Aspergillus* sp. and *Fusarium* spp. *Candida albicans* remains the most important although others such as *C. glabrata, C. tropicalis, C. dubliniensis* and *C. krusei* are being increas‐ ingly detected [33]. *Aspergillus* sp. (*A. fumigatus* followed by *A. flavus*) have been reported less frequently than *Candida* sp., but Aspergillus endophthalmitis cause rapidly progressive retinal damage and is more visually devastating compared to Candida endophthalmitis [34]. Com‐ mon causes of endogenous bacterial endophthalmitis include *S. aureus*, *B. cereus* and Gramnegative organisms, including *Escherichia coli*, *Neisseria meningitidis* and *Klebsiella* spp. [10]. *Bacillus* spp. is a primary cause of endogenous endophthalmitis in intra-venous drug abusers due to contaminated injections and drug solutions [10]. Rarely, protozoa like Microsporidia and Amoebae may be the pathogens for endogenous endophthalmitis [35]. It is seen that visual outcomes are poorer with endogenous fungal endophthalmitis compared to endogenous bacterial endophthalmitis. The common foci of infection may be urinary tract infection, septic arthritis, pneumonia and endocarditis [35]. Seriously ill patients may neglect eye symptoms until vision is permanently compromised. Hence, it has been recommended that ophthalmic screening should be routine in high-risk situations such as intra-venous drug use, long-term antibiotics, immunosuppressive therapy, primary or secondary immunodeficiency, prolonged central line use, debilitated patients and pre-mature infants [36].

#### *3.3.1. Endophthalmitis associated with microbial keratitis*

16]. Bacterial infections are the most common cause of post-operative endophthalmitis, and Gram-positive isolates account for the majority of these cases [2]. Coagulase negative *Staphy‐ lococcus* accounts for majority of cases followed by *enterococci* and *streptococci* of viridans group. Among Gram-negative isolates, *Pseudomonas aeruginosa* endophthalmitis is identified [17, 18]. Fungal infections are less common and occur particularly in association with the use of contaminated ocular irrigation fluids [19]. *Candida* spp. (especially *C. parapsilosis*), *Aspergillus* spp. and *Fusarium* spp. are common fungal pathogens responsible for post-operative endoph‐ thalmitis [20]. *E. faecalis* is the causative agent in 4% to 8% of post-operative endophthalmitis cases and is isolated most frequently from infected filtering blebs following glaucoma surgery [10]. The visual outcome is poor and has become a key public health concern because of the

emergence of antibiotic resistance to useful antibiotics including vancomycin [21].

with glaucoma filtering surgery [26].

24 Advances in Common Eye Infections

**3.2. Post-traumatic endophthalmitis**

**3.3. Endogenous endophthalmitis**

Delayed onset infection (> 6 weeks post-operative) may occur due to sequesteration of lowvirulence organisms introduced at the time of surgery or to delayed inoculation of organisms [22, 23]. *S. epidermidis*, *Propionibacterium acnes*, filamentous bacteria (including *Actinomyces* and *Nocardia* sp.), *Hemophilus influenzae*, non-tuberculous mycobacteria (*M. abscessus, M. chelonae* etc.) and *candida* spp. are responsible for chronic or delayed endoph‐ thalmitis [24, 25]. In cases with delayed onset infection, organisms gain access to the eye through either wound abnormalities, suture tracks or filtering blebs. It is more common

Penetrating injuries are accompanied by higher infection rate of 1–17% compared to postsurgery cases [10]. The broad prevalence range is due to factors such as frequency of intraocular foreign bodies, distribution of trauma causes, and management strategies. Onset may be acute or delayed, but the most virulent organisms can destroy an eye within hours. Important risk factors for post-traumatic endophthalmitis are the presence of an intra-ocular foreign body (IOFB), the length of time between injury and foreign body removal, delay in closure of the globe, poorer visual acuity at presentation, virulence of organisms and the immune system of the affected individual [27]. Post-traumatic-endophthalmitis-associated isolates are mostly derived from the environment, and hence includes greater variety of organisms than those following ocular surgery. *Staphylococcus* and *Streptococcus* sp. are the most frequent pathogens, followed by *Bacillus cereus and P. aeruginosa* [28]. Filamentous fungi, especially *Aspergillus* sp. and *Fusarium* sp., are also responsible for post-traumatic endoph‐ thalmitis [29]. Bacillus infection is noteworthy as it causes rapid destruction of eye leading to decline in retinal function and vision loss within 24 to 48 h post-infection, despite aggressive treatment and/or surgical intervention. This suggests that even if the infected eye is rendered sterile by antibiotics, ocular damage continues to occur due to the bacterial toxins produced –

Endogenous endophthalmitis is relatively rare accounting for 2% to 8% of all endophthalmitis cases [31]. It results from the introduction of organisms into the eye as a result of haematoge‐

haemolysins, lipases, enterotoxins and proteases – acting together [30].

Cornea gets infected in situations like contact lens wearer, any pre-existing corneal disease and rarely due to dry cornea (as seen in chronic blepharoconjunctivitis or dacrocystitis, tear film deficiency or topical steroid therapy). If corneal infection is severe enough to cause progressive ulceration of cornea, then it can lead to bacterial endophthalmitis [11].

The incidence rates [37, 38] and etiologial agents of different types of endophthalmitis have been enumerated in Tables 2 and 3, respectively.



**Table 2.** Incidence rates of different types of endophthalmitis


**Table 3.** Etiological agents of different types of endophthalmitis
