Continuing Education Activity

Endophthalmitis is defined as an inflammation of the inner coats of the eye, resulting from intraocular colonization of infectious agents with exudation within intraocular fluids. It is a potentially blinding condition. The category or type of endophthalmitis such as postoperative, post-traumatic, or endogenous, etc. influences the clinical presentation, microbiology, and visual outcome. If left untreated or inadequately treated, it progresses to panophthalmitis requiring evisceration or enucleation of the eyeball. This activity reviews the evaluation and treatment of endophthalmitis and highlights the role of the interprofessional team in evaluating and treating patients with this condition.

Objectives:

• Describe the pathogenesis of endophthalmitis.
• Summarize the relevant history and physical examination of patients with endophthalmitis.
• Review the evaluation process of patients with endophthalmitis.
• Outline the interprofessional care of patients with endophthalmitis.

Introduction

Endophthalmitis is defined as an inflammation of the inner coats of the eye, resulting from intraocular colonization of infectious agents with exudation within intraocular fluids (vitreous and aqueous).[1] Based on the mode of entry of the organism, it is divided into 'exogenous' and 'endogenous.' Depending on the causative event, the exogenous endophthalmitis can be either post-traumatic or postoperative.[2] Some of the definitions used in endophthalmitis are listed in figure 1 (classification of endophthalmitis). Unless diagnosed and treated promptly, acute endophthalmitis can lead to severe vision loss. The category or type of endophthalmitis such as postoperative, post-traumatic or endogenous, and others influence the clinical presentation, microbiology, and visual outcome. Endophthalmitis is one of the most serious ophthalmic emergencies which require urgent medical attention and treatment to save the vision or to salvage the integrity of the eye.

Etiology

Depending on the infectious agent producing endophthalmitis, two important categories are recognized, bacterial and fungal endophthalmitis. In a recent study on microbial causes of all types of endophthalmitis, 85.1% of all isolates were due to gram-positive bacteria, 10.3% due to gram-negative bacteria, and 4.6% of all cases were due to fungi.[3] The most common bacterial pathogens isolated are Staphylococcus epidermidis (30.3%), other coagulase-negative Staphylococcus (9.1%), Streptococcus viridans (12.1%), Staphylococcus aureus (11.1%), Enterobacteriaceae (3.4%), and Pseudomonas aeruginosa (2.5%).[3] 

The predominant organism depends on the source (vegetable matter or retained intraocular foreign body), route of spread (post-surgery, trauma, or delayed onset or hematogenous dissemination), geographic location, and patient characteristics.

In cases of post-traumatic endophthalmitis, Staphylococci and Bacillus cereus are the most common isolates.[4] 

Acute postoperative endophthalmitis (within 6 weeks of surgery) results most commonly due to contamination of the intraocular structures with normal bacterial flora of the adnexa such as Staphylococcal epidermidis. 

Delayed or chronic post-cataract surgery endophthalmitis (after 6-week of surgery) is characterized by slow course and panuveitis like picture with granulomatous keratic precipitates, inflammatory deposits over the IOL (intraocular lens), white capsular plaque, anterior chamber reaction, vitritis, and cystoid macular edema (CME) which may respond to periocular or systemic steroid but usually recurs.[5]  The common causative organism is usually bacterial (most commonly Propionibacterium acnes followed by Coagulase-negative Staphylococcus), though fungal infections (including Aspergillus, Candida, and others) can also occur.[6]

In cases of delayed onset, endophthalmitis associated with bleb (trabeculectomy)/glaucoma drainage implants Streptococci species, and Haemophilus are the predominant culture isolates.[7][8]

The most common organisms isolated in post intravitreal injection endophthalmitis are coagulase-negative staphylococci followed by streptococci.[9] 

In certain conditions, exogenous endophthalmitis can occur without a full-thickness breach in ocular coats. For example, after scleral buckling (due to buckle exposure or secondary infections), secondary to contact lens keratitis, and post LASIK.[10][11][12]

Most cases of endogenous endophthalmitis are secondary to fungemia (predominantly Candida species). Among bacterial causes, staphylococcal species predominate in the western population, and among the East Asian population, Klebsiella pneumoniae predominates.[13] Pseudomonas is a virulent and aggressive organism that can also cause endogenous endophthalmitis.[14]

Endophthalmitis after infectious keratitis is usually bacterial (usually Pseudomonas aeruginosa, Staphylococcus sp, and Streptococcus sp), though fungal endophthalmitis (including Aspergillus sp, Fusarium sp) may also occur.[15][16]

Epidemiology

The relative frequency of various subtypes of endophthalmitis varies depending upon the geography, level of specialization at the ophthalmic center, and study duration. For example, studies before 2005 have very few cases of post intravitreal anti-VEGF (vascular endothelial growth factor) injection endophthalmitis as anti-VEGF agents received first FDA approval in 2004.

In a recent retrospective cohort study in the U.S., acute onset endophthalmitis occurred in 0.04% of cataract surgeries and 0.016% of patients receiving an intravitreal injection.[17][18] The incidence of post-traumatic endophthalmitis varies from 0.9% to 17%.[19][20] 

Case series from Asian countries have reported an incidence of 0.023% to 0.076% of endophthalmitis in post-cataract surgery setting and 0.01% to 0.10% post intravitreal injections.[21][22][23][24] 

Among the intraocular surgeries, secondary intraocular lens implantation seems to have a very high risk (0.36%) for acute endophthalmitis, and trabeculectomy may have a high risk (1.8%, maybe up to 5.7%) for delayed or late-onset endophthalmitis especially after the advent of mitomycin-C or 5-fluorouracil.[2][25][26]

Endophthalmitis after pars plana vitrectomy had the lowest rates (0.046%) when compared with other ocular surgeries [secondary IOL-0.366%, combined penetrating keratoplasty (PK) with cataract surgery- 0.194%, PK- 0.178%, glaucoma surgeries -0.124%, combined trabeculectomy and cataract surgery- 0.114%, overall incidence after intraocular surgery-0.093%, and cataract surgery with or without IOL-0.082%] in a study.[25] 

There is no significant difference in the rates of endophthalmitis after intravitreal injection of various anti-VEGF agents.[27][28] Cluster endophthalmitis cases have occurred after intravitreal use of bevacizumab due to either lapse in the cold chain, sub-optimal compounding of bevacizumab aliquots, or fake drug.[29][30]

Pathophysiology

The most critical factor in the causation of endophthalmitis is the breakdown of the ocular blood barrier and intraocular colonization by pathogens (bacteria/fungi). In exogenous endophthalmitis, the inciting injury or surgery causes disruption of globe integrity, which allows invasion of the pathogens. In rare cases of delayed postoperative endophthalmitis, the organisms (usually Propionibacterium acnes sequestered in the capsular bag after cataract surgery) may get released after YAG capsulotomy causing endophthalmitis.[31] In endogenous endophthalmitis, common sources of bacteremia and fungemia include endocarditis, urinary tract infections, intravenous infusions, indwelling catheters or invasive procedures, liver abscess, and others.

The pathogen's ability to cause intraocular damage depends on its virulence and host response. The virulence of an organism depends on:

• Its ability to synthesize toxic factors such as hemolysin BL, cytolysin, pneumolysin, lipopolysaccharide (bacterial outer envelope), and others[32][33][34][35]
• The rapidity of intraocular growth[36] 
• Motility of organism[37] 

The ability of the host's innate immunity to mount an effective inflammatory response depends on the virulence of the organism. The acute inflammatory response may clear the less virulent organism; However, more virulent organisms may evade the host's immune response by secreting toxins or biofilm around it, in which case the inflammatory response can result in damage to intraocular tissues and loss of vision. The peak of inflammatory mediators such as TNFα, interleukin 1-beta, interferon-gamma coincides with increased inflammatory signs such as fibrin in the anterior chamber, iris synechiae formation, hypopyon, and loss of the red reflex.[38] The elevated levels of complement factors in aqueous and vitreous in cases of intraocular infection contribute to the damage of the uveoretinal tissue.

History and Physical

In typical postoperative endophthalmitis, poor visual acuity, corneal edema, hypopyon, vitreous inflammation, and poor fundus visualization are the most common clinical signs.[39]

Reduced vision and worsening pain - In Endophthalmitis Vitrectomy Study (EVS) study, reduction in vision and pain accounted for 94% and 74% of all symptoms while in the ESCRS study, it accounted for 92.9% and 79% of all symptoms.[40][41][40] These studies show that though pain is a significant diagnostic sign, pain can be absent in up to 25% of cases. The other common presenting features are swollen eyelid, redness of the eye, circumcorneal congestion, photophobia, ocular discharge, fibrinous membranes in the anterior chamber, iris synechiae formation, loss of fundal red reflex, and floaters. Bleb-related endophthalmitis initially presents as bacterial conjunctivitis with signs and symptoms such as conjunctival hyperemia and discharge, yellowish colored filtering bleb, and variable anterior chamber inflammatory reaction, which later progresses to involve the posterior chamber as well. Certain signs, if seen such as corneal ring abscess, are highly suggestive of Bacillus, while gas bubbles in the anterior chamber, amaurosis, or green-brown hypopyon indicate Clostridium.[42][43] 

In chronic endophthalmitis, patients present with low-grade anterior chamber inflammation and vitritis. Visual acuity can remain preserved until late in the presentation. Organisms such as Propionibacterium tend to get localized within the capsular bag and present as posterior capsular plaque.[44] The vital history that should raise suspicion of chronic endophthalmitis following keratitis or intraocular surgery is prolonged uveitis in a subject with no previous history of inflammation and either inadequate response to topical steroids or inability to wean them.[45]

In patients with endogenous endophthalmitis, the presentation can be bilateral with systemic morbidities like sepsis, nausea, vomiting, and fever. Endogenous bacterial endophthalmitis presents with pain, blurred vision, and redness with a variable degree of both anterior chamber and vitreous involvement. A subretinal abscess may be noted.[46] Endogenous fungal endophthalmitis presents initially as focal choroiditis or chorioretinitis, which later extends into the vitreous cavity. Retinal vascular sheathing and vascular occlusion may be present with satellite lesions in certain conditions.[47] 

Endophthalmitis after infectious keratitis presents with hypopyon and severe visual loss, sometimes with an inaccurate projection of rays. Ultrasound evaluation of the posterior segment can help to detect vitreous involvement in the form of echoes in the vitreous and confirm the diagnosis.

Progression of the disease may lead to panophthalmitis, corneal infiltration and perforation, and phthisis bulbi.

Due to severe damage to ocular structures, the workup of endophthalmitis is done on an emergency basis.

History 

1. Inciting event – surgery/trauma/contiguous spread (keratitis)/endogenous endophthalmitis/other procedure
2. Onset – fulminant/acute/chronic: Most cases of fulminant endophthalmitis are caused by highly virulent organisms such as Pseudomonas aeruginosa / Bacillus species (see figure on the classification of endophthalmitis)
3. The rapidity of progression – Rapid or gradual: Bacterial endophthalmitis progresses faster than fungal endophthalmitis.
4. Systemic illness – history of intravenous infusion, prolonged hospitalization, diabetes, renal or liver problems: Helps to localize any source of endogenous endophthalmitis, calibrating drug dosage.

Ophthalmic Assessment

Clinical

1. Visual acuity including projection of rays- When visual acuity is less than counting fingers, EVS standards help in the maintenance of uniform records. After occluding the better eye, with light directed from behind the patient: 

Hand movements are tested at a distance of 60 cm

Perception of light is tested at a distance of 90 cm with the bright light of indirect ophthalmoscope

At least four out of five responses should be correct for reading to be considered.

2. Examination of the ocular adnexa- especially to look for severe blepharitis, meibomitis, stye, chronic dacryocystitis, and other sources of infection3. Ocular movements- Reduced or absent ocular movements in a case of endophthalmitis with proptosis and pain, clinically point to the diagnosis of panophthalmitis4. Anterior segment examination [close focus at the sites of entry – SICS(small incision cataract surgery) tunnel/ Corneal entry wound / Bleb/ perforating trauma] look for corneal clarity; corneal infiltrate, Posterior capsular plaque, vitreous in the wound, open wound, unsutured wound, hypopyon, fibrin, posterior synechia5. Intraocular pressure6. Fundus examination (dilated) if media permits to look for any specific pattern as well as mimics such as dropped lens matter/ intraocular foreign body (IOFB)

Grading of vitreous haze (EVS standard) [clinical examination with an indirect ophthalmoscope][40]

• Grade 1: More than 20/40 (6/12) view of the retina
• Grade 2: Second order retinal vessels are visible
• Grade 3: Some vessels visible but not the second-order vessels
• Grade 4: No retinal vessels are visible, only red reflex present
• Grade 5: No red reflex is seen

Evaluation

 Imaging

1. Slit-lamp photography to document
2. Fundus photographs- especially ultra-widefield imaging (Optos) using scanning laser ophthalmoscope principle which can image through the small pupil and vitreous haze[48][49]
3. Fundus fluorescein angiogram (FFA) if the fundus is visible- May help to rule out other diseases
4. Optical coherence tomography (OCT)- When fundus is visible, OCT can help to characterize the location and other characteristics of retinochoroidal or vascular involvement
5. Anterior segment OCT in case of endophthalmitis after infective keratitis and others
6. Ultrasound B scan – Endophthalmitis gives rise to vitreous inflammation, which is seen as point echoes in the vitreous cavity with mild to moderate amplitude. Ultrasound examination is also used to look for other features, including retinochoroidal thickening, posteriorly dislocated lens/IOL, concomitant retinal detachment, choroidal detachment, or IOFB, to follow up vitreous inflammatory reaction serially post intravitreal injection. A subretinal abscess at the macula may be present, especially in endogenous endophthalmitis.
7. CT scan orbits to look for IOFB in post-trauma cases

Ocular Sampling

1. Anterior chamber tap

With the patient looking straight, a 30G/27G needle is introduced via a selected site on the peripheral cornea tangentially keeping direction parallel to the iris, with the needle directed towards exudate/hypopyon. With active suction, 0.1 to 0.2 cc of aqueous/exudate is aspirated. A cotton tip applicator is applied, and the needle is removed.

 2. Vitreous tap/biopsy

Vitreous cultures usually produce more accurate results than do aqueous cultures.[50] 

Vitreous Tap

A 26 G needle is connected to a 2 cc syringe and is entered through pars plans (3 mm behind limbus in aphakic, 3.5 mm behind limbus in pseudophakic, and 4 mm behind the limbus in phakic). A sample of 0.2 to 0.3 cc is aspirated. It is controversial in non-vitrectomized eyes due to the possibility of vitreous traction and subsequent retinal detachment. In such cases, vitreous biopsy via vitrectomy cutter is preferred.

Vitreous biopsy

This can be obtained via one port vitrector or by combining it with a three-port diagnostic/ therapeutic pars plana vitrectomy. A 5 ml syringe is connected to the suction port of the vitrectomy cutter, and once the cutter port is visualized through the pupil, the surgical assistant aspirates, without starting the infusion. At the same time, the surgeon activates the cutter until the eye softens visibly. When combined with a three-port vitrectomy, the fluid infusion is turned on once the sample has been collected as described.

Samples are sent for microbiological and molecular diagnostic (PCR) testing. Though PCR allows improved pathogen detection even with low pathogen counts, cost, increased risk of contamination, lack of antibiotic sensitivity testing, lack of quality control standards limit its widespread usage.[51] 

The standard microbiological procedure includes smear preparation for specific stains and inoculation of selective culture media for recovery of intraocular pathogens and antibiotic sensitivity testing. Commonly used stains and culture media are elaborated in figure 2 (commonly used stains and culture media for the detection of microbial agents).

Systemic Assessment 

1. Look for signs of septicemia – fever, elevated ESR (erythrocyte sedimentation rate)
2. Blood culture in cases of endogenous endophthalmitis
3. Blood tests – hemogram, renal, and liver function tests (to look for drug toxicity)
4. Search for the focus of infection in endogenous endophthalmitis

Treatment / Management

Endophthalmitis is a true ophthalmic emergency and requires appropriate and prompt therapy. The main objectives in endophthalmitis treatment are:

1. To eradicate or control infection
2. Management of inflammation
3. Supportive therapy

1. To Eradicate or Control Infection

A. Systemic Antibiotics

The use of systemic antibiotics in the setting of exogenous endophthalmitis is controversial as most of the drugs given have poor intraocular penetration. The best-documented drugs achieving therapeutic levels in vitreous are fourth-generation fluoroquinolones[52], meropenem, and linezolid.[53]

EVS study used ceftazidime 2 g every 8 hourly, amikacin 7.5 mg/kg initial dose followed by 6 mg/kg every 12 hourly. EVS study has concluded that the use of systemic antibiotics does not affect the final visual outcome in postoperative endophthalmitis.[40]

In endogenous endophthalmitis, systemic antimicrobials, in conjunction with intravitreal antimicrobials, reduce the rates of evisceration or enucleation.[54] 

B. Local Antibiotics (topical/subconjunctival)

A combination of two drugs is preferred during the initial presentation, one having a potent effect on Gram-positive organisms and another on Gram-negative organisms. Once antibiotic sensitivity is determined, targeted intervention is done. In the presence of corneal ulcer or wound abscess, fortified drops (including cefazolin 5% and tobramycin 1.4%) are used. Sub conjunctival antibiotic injections are not routinely used due to issues with patient comfort, subconjunctival hemorrhage, and watering from the eye.

EVS study used vancomycin (25 mg/0.5 ml), ceftazidime (100 mg/0.5 ml) for subconjunctival injection, and topical vancomycin (50 mg/ml) and amikacin (20 mg/ml) every 4 hourly for routine cases or every hour if wound leak was present.[40]

C. Intravitreal Injections

The intravitreal route of drug administration helps in achieving high concentrations of the drug in the vitreous cavity without associated systemic side effects. It is essential to ensure the proper dosage of the drug. While inadequate doses cause treatment failure, the excess dose can cause toxic effects on the retina. Two broad-spectrum antibiotics are chosen initially, EVS study utilized intravitreal vancomycin (1 mg/0.1 ml) and amikacin (0.4 mg/0.1 ml).[40] However, due to the higher retinotoxic potential of amikacin, it has been superseded by ceftazidime (2.25 mg/0.1 ml). Commonly used drugs in the treatment of endophthalmitis and their concentrations are enumerated in figure 3 (Commonly used antibiotics in the treatment of endophthalmitis). Intravitreal gentamicin can cause macular infarction.[55] 

Recently, there is a trend towards the use of other intravitreal antibiotics such as:

• Ampicillin 5000 mcg/0.1 ml[56]
• Piperacillin/tazobactam 225 mcg (piperacillin 200 mcg and tazobactam 25 mcg/0.1 ml)[57]
• Imipenem/cilastatin (rabbit 50 to 100 mcg and 50 to 100 mcg/0.1ml)[58]
• Carbenicillin (rhesus monkey, 1000 mcg/0.1 ml)[59] 
• Ticarcillin 3000 mcg/0.1 ml in albino rabbits[60]
• Cefazolin 2250 mcg/0.1 ml,[56]
• Cefotaxime 400 mcg/0.1 ml[56]
• Ceftriaxone 2000 mcg/0.1 ml[61]
• Cefuroxime 1000 mcg/0.1 ml[61]
• Clindamycin 1000 mcg/0.1 ml[61]
• Levofloxacin 625 mcg/0.1 ml[56]
• Moxifloxacin 500 mcg/0.1 ml[62] ( from the sterile moxifloxacin drop 0.5%, the reported patient had vitrectomized eye)
• Ciprofloxacin 100 mcg/0.1 ml[56]
• Aztreonam 100 mcg/0.1 ml[56]
• Colistin 100 mcg/0.1 ml[63][56][61]

Viruses usually do not cause suppurative inflammation of the eye or endophthalmitis, and rather they cause retinitis, which may be associated with retinitis. Many of such cases are treated by specific antivirals

D. Vitrectomy

Vitrectomy has several advantages over conservative therapy. Vitrectomy improves retinal oxygenation, reduces the inflammatory load within the eye, provides specimens for diagnostic evaluation, allows direct inspection of the retina, allows definitive treatment, reduces the load of infection, and reduces the severity of the disease, and accelerates visual rehabilitation.[64] There are two schools of thought: one based on EVS study and another based on complete and early vitrectomy for endophthalmitis (CEVE) study.[40][64] 

According to the EVS study, vitrectomy was better than vitreous tap and intravitreal antibiotics for the most severe cases, i.e., for patients with initial presenting vision being the perception of light alone, and vitrectomy, if performed, is limited to core vitrectomy without inducing posterior vitreous detachment. Contrary to the EVS study, CEVE (complete and early vitrectomy for endophthalmitis) advocates complete vitrectomy, which includes induction and removal of posterior vitreous to prevent exudates from settling over the macula. However, in the periphery, the surgeon must be conservative to avoid iatrogenic break formation. 

In delayed-onset endophthalmitis secondary to propionibacterium acnes, pars plana vitrectomy is combined with total capsulectomy and IOL exchange/removal or wash of the capsular bag with antibiotics.[44] 

2. Management of Inflammation

Corticosteroids are the most potent anti-inflammatory agents used in the management of endophthalmitis. To be useful, they must be given early and in appropriate doses. They should, however, not be used in fungal endophthalmitis as it enhances fungal growth by weakening defense mechanisms within the body. They can be used either as an intravitreal injection, topical drops, or systemically.

The most commonly used corticosteroid intravitreally is dexamethasone (0.4 mg/ 0.1 ml). However, there is no clear consensus regarding the role of intravitreal corticosteroids.[65] Topical steroids can penetrate an intact cornea, and their efficacy is proportional to the frequency of installation. Systemic steroids are preferred at a dose of 1 to 1.5 mg/kg body weight administered in three divided doses to achieve uniform concentration during the day, unlike in chronic uveitis where once a day regimen is preferred.[66]

EVS study utilized only topical (prednisolone acetate 1% eye drops), subconjunctival (dexamethasone 6 mg/0.25 ml), and systemic steroids (prednisolone 30 mg twice a day for 5 to 10 days).[40]

3. Supportive Therapy

Cycloplegic agent (homatropine 2%, atropine 1%) is an essential part of treatment that relieves ciliary spasms and prevents synechiae formation.

In patients with elevated intraocular pressure, oral and topical medications need to be added. Vitreous tap before intravitreal injection also reduces intraocular pressure.

Hypertonic saline (5% drop or 6% ointment) may be needed in cases of severe corneal edema.

Prophylaxis

Endophthalmitis cannot be prevented entirely, but due to various measures taken in recent times, its incidence has come down. Most of the cases of endophthalmitis are exogenous, which prompts for taking prophylactic action. 

Proposed measures as prophylaxis of postoperative endophthalmitis include preoperative 5% povidone-iodine antisepsis of conjunctival cul de sac, check for lid infections preoperatively, checking the patency of nasolacrimal duct, use of intracameral cefuroxime 1000 mcg/0.1 ml[67][41] (according to the guideline by European society for cataract and refractive surgery)[68]/moxifloxacin (0.5% weight by volume from the sterile moxifloxacin drop 0.5%)[69][70]at the end of the surgical procedure, prompt repair of conjunctival erosions, leaking blebs.[71]

 A large study on 2 million eyes undergoing cataract surgery in the Aravind Eye Care System showed that intracameral moxifloxacin reduced the incidence of postcataract surgery endophthalmitis, especially in cases with complicated cataract surgery with posterior capsular rent.[70]

However, caution needs to be exercised regarding the use of intracameral antibiotics, as there are reports of retinal toxicity with certain antibiotics. For example, hemorrhagic occlusive retinal vasculitis (HORV) has been reported after the use of intracameral vancomycin.[72]

The most common contaminants in cases of post-intravitreal injections are streptococci, which are common members of oral flora, and oral flora bacteria may be aerosolized during the speech. The use of masks and adhering to a strict no-talking policy has been noted to be effective in reducing the overall incidence of post-injection endophthalmitis and particularly the incidence of streptococcal endophthalmitis.[73][74][73]

Prompt surgical repair of open globe injuries and prophylactic intravitreal injection of antibiotics (particularly in the setting of retained intraocular foreign body) with or without systemic antibiotics have been associated with reduced rates of post-traumatic endophthalmitis.[75][76]

Differential Diagnosis

Post-surgical Endophthalmitis

1. Toxic anterior segment syndrome (TASS) is an acute inflammatory condition presenting within 24 hours of surgery with a severe anterior chamber reaction, limbus to limbus corneal edema. However, there is no adnexal involvement, and the patient responds dramatically to the addition of steroids.[77] Various features differentiating TASS from acute postoperative endophthalmitis are listed in figure 4 (common differentiating features of TASS with endophthalmitis).
2. Posteriorly dislocated lens matter
3. Fibrinous reaction post vitrectomy
4. Phacoanaphylaxis etc.

Non-surgical Endophthalmitis

1. Chronic uveitis – certain cases of chronic indolent endophthalmitis may be confused for chronic panuveitis.
2. Retained intraocular foreign body
3. Old vitreous hemorrhage
4. Toxoplasma retinochoroiditis
5. Necrotic retinoblastoma 
6. Acute retinal necrosis
7. Severe panuveitis
8. Seasonal hyperacute panuveitis (SHAPU)
9. Intravitreal cysticercus with intraocular inflammation

Prognosis

Visual outcome in a patient with endophthalmitis depends on various variables.

• Nature of endophthalmitis: Better visual acuity has been reported in cases with culture-negative post-surgical endophthalmitis.[78] Bleb-associated endophthalmitis carries a poor visual prognosis.[79] Endogenous bacterial and fungal endophthalmitis also carries a poor visual prognosis.[54][80]
• Organism: Endophthalmitis due to Streptococcus,[78] Bacillus,[81] Pseudomonas,[82] and Candida[83] carry poor visual prognosis. 
• Presenting visual acuity: In the EVS study, it has been noted that presenting visual acuity remains more powerful than microbiological factors in predicting visual outcome and response to vitrectomy.[40]
• Time to initiation of appropriate therapy: It is of utmost importance in cases of post-traumatic endophthalmitis, especially with Bacillus species.[84] In the EVS study, in the group with a vision of light perception only, early vitrectomy resulted in a three-fold increased chance to achieve ≥ 20/40 (33%), a two-fold increased chance to achieve ≥ 20/100 (56%) and was less likely to worsen <5/200 (20%).[40]
• Systemic stability of the patient: Immunocompromised patients, patients with endogenous endophthalmitis, have concurrent polymicrobial infections which influence the final outcome.[54] 

In the EVS study in post-cataract surgery endophthalmitis, it was noted that only 53% of treated eyes had final visual acuity of 20/40 or better, and 15% had a final visual acuity of 20/200 or worse.[40] 

If left untreated or inadequately treated, endophthalmitis progresses to panophthalmitis, requiring evisceration or enucleation of the eyeball. It is noted that patients suffering from a corneal ulcer, endogenous endophthalmitis, and low visual acuity are at higher risk of requiring evisceration or enucleation.[85]

Complications

• Panophthalmitis
• Glaucoma
• Orbital cellulitis
• Intracranial spread
• Septicemia
• Loss of vision 
• Phthisis
• Hypotony
• Painful blind eye

Deterrence and Patient Education

Patients should be explained about the warning signs of endophthalmitis such as pain, redness of the eye and blurring of vision, etc. at discharge after any intraocular procedure. Early detection and prompt treatment are the key. Patients should be explained the seriousness of the condition and the need for intensive pharmacotherapy.

Enhancing Healthcare Team Outcomes

Most cases of endophthalmitis are exogenous and are seen in the postoperative period. Patients with uncontrolled blood sugar levels, high temperature (can be secondary to underlying septicemia) are prone to postoperative endophthalmitis. Hence the nursing staff and physician must check for systemic stability before any surgical procedure to reduce the chances of postoperative endophthalmitis. Nursing staff posted at the daycare or inpatient ward should look for preoperative risk factors such as blepharitis, dacryocystitis, open wound, etc. before shifting the case to the operating room. Nursing staff plays a vital role in monitoring the patient, charting the vital parameters, and reporting the issues to the treating physician. Certain cases with fulminant endophthalmitis might require evisceration/ enucleation; hence pre-surgical counseling of patients by a psychiatrist helps to reduce the morbidity. Cases with endogenous endophthalmitis have systemic comorbidities such as invasive aspergillosis or chronic renal failure with prolonged catheterization, etc., and hence may not primarily present to the ophthalmologist with ocular complaints. Therefore specialists other than an ophthalmologist must be aware of such an entity and promptly refer such cases to improve outcomes.