**3. Presenting features of endophthalmitis and diagnosis**

An eye with inflammation that is out of proportion to the predicted post-operative clinical course or previous trauma than expected should be suspected of having endophthalmitis. [1-3, 12] Majority of patients with post-operative endophthalmitis present with an acute on‐ set usually within a week after surgery. [12] Most common presentations include decreased vision, ocular pain, photophobia, redness, corneal edema, hypoyon and vitritis (Figure 2). In addition, retinal vasculitis, retinal hemorrhages, and posterior pole hypoyon may also occur. Chronic post-operative endophthalmitis is characterized by insidious inflammation and ap‐ pears less common than the acute type. Patients with chronic post-operative endophthalmi‐ tis usually present several weeks after surgery and often these patients have infection with less virulent bacterial and fungal pathogens. [13]

Progressive vitritis is one of the key findings in cases of infectious and non-infectious en‐ dophthalmitis, and in the vast majority of cases, a hypopyon can be seen at the time of initial presentation. [2, 3] Absence of a fundus red-reflex, presence of relative afferent pupillary de‐ fect (RAPD) and light perception vision at the time of initial presentation may be associated with worse final visual outcome (Figure 3). Infections with virulent organisms present with

**Figure 2.** Anterior chamber reaction and hypopyon in a patient with endophthalmitis.

(a) (b)

traumatic eye injury (b) after injury.

174 Common Eye Infections

**2. The etiology of endophthalmitis**

rest 17% may be due to fungal infection. [2, 3, 10, 11]

less virulent bacterial and fungal pathogens. [13]

**3. Presenting features of endophthalmitis and diagnosis**

**Figure 1.** Signs of early post-operative endophthalmitis in patients after intraocular surgery (a) and after repair of

The spectrum of the microorganisms causing endophthalmitis may differ in different parts of the World. According to the Western literature, over 75% of culture positive cases of en‐ dophthalmitis are due to Gram-positive bacteria that includes, Staphylococcus species, Streptococcus species, Enterococcus species, and other Gram-positive species. [2, 3] Gramnegative species may account for up to 6% of endophthalmitis cases. Studies from other countries such as India reveal that Gram-positive bacteria may account for 53% of post-oper‐ ative cases of endophthalmitis and up to 26% may be due to Gram-negative bacteria, while

An eye with inflammation that is out of proportion to the predicted post-operative clinical course or previous trauma than expected should be suspected of having endophthalmitis. [1-3, 12] Majority of patients with post-operative endophthalmitis present with an acute on‐ set usually within a week after surgery. [12] Most common presentations include decreased vision, ocular pain, photophobia, redness, corneal edema, hypoyon and vitritis (Figure 2). In addition, retinal vasculitis, retinal hemorrhages, and posterior pole hypoyon may also occur. Chronic post-operative endophthalmitis is characterized by insidious inflammation and ap‐ pears less common than the acute type. Patients with chronic post-operative endophthalmi‐ tis usually present several weeks after surgery and often these patients have infection with

Progressive vitritis is one of the key findings in cases of infectious and non-infectious en‐ dophthalmitis, and in the vast majority of cases, a hypopyon can be seen at the time of initial presentation. [2, 3] Absence of a fundus red-reflex, presence of relative afferent pupillary de‐ fect (RAPD) and light perception vision at the time of initial presentation may be associated with worse final visual outcome (Figure 3). Infections with virulent organisms present with aggressive signs and symptoms of endophthalmitis. Other risk factors associated with worse visual outcome may include presence of corneal infiltrate, wound abnormalities after cata‐ ract surgery and virulent pathogens. According to the Endophthalmitis Vitrectomy Study (EVS), [10] a prospective, randomized clinical trial of post-operative acute endophthalmitis, hypopyon was documented in 75% of the enrolled patients and according to the European Society of Cataract and Refractive Surgeons Endophthalmitis Study (ESCRS), hypopyon was present in 72% of patients having endophthalmitis. [11, 14] Pain was absent in almost onefourth of patients enrolled in the EVS at the time of their initial presentation. Untreated en‐ dophthalmitis may lead to panophthalmitis which may present with increased pain, proptosis, limitation of eye movements, eyelid edema, intense conjunctival chemosis, cor‐ neal edema, infiltrate, complete anterior chamber hypopyon and even eye perforation. [15]

Patients having full blown endophthalmitis within days after the surgery often have infec‐ tion due to Staphylococcus or Streptococcus species or alpha-hemolytic Streptococci species of the 'viridans' group during which vision can be lost over 12 hours if no intervention is undertaken. [10, 16-18] A diagnosis of endophthalmitis should be entertained for any pa‐ tient presenting within 6 weeks after surgery with pain and loss of vision. In most cases, the diagnosis of endophthalmitis is made on clinical grounds. Ultrasonography is necessary for the clinical evaluation of patients with suspected infectious endophthalmitis in the absence of a good fundus view. Rapid detection and identification of the causative pathogens is cru‐ cial for vision-saving treatment. [19] Conjunctival and corneal swabs are usually not helpful, as the correlation with the microorganisms isolated is very low. [2, 10, 11, 18] Similarly, mi‐ croorganism identification from the anterior chamber is less successful as compared to vitre‐ ous tap in cases of suspected endophthalmitis. Depending on the visual acuity, an anterior chamber tap and a vitreous tap along with intra-vitreal antibiotics may be indicated to con‐ firm the infection and treat the cause. Samples of aqueous and vitreous should be collected

**Figure 3.** External photograph of a patient with history of cataract surgery who presented with severe conjunctivitis, corneal opacification and vascularization was found to have evidence of endophthalmitis.

from these patients for Gram staining, culture, and Polymerase Chain Reaction (PCR) assay. [20] Anterior chamber and vitreaous specimens obtained should be directly inoculated on to the culture media at the time of procedure. If any of these investigations yield a positive re‐ sult, the case can be classified as a proven case of infective endophthalmitis; otherwise the case should be classified as presumed unproven endophthalmitis. Each unproven case should be carefully considered if there is evidence of the Toxic Anterior Segment Syndrome (TASS) or non-infective uveitis when the case is not considered infective otherwise. [21, 22]

Patients presenting late after surgery with uveitis that has not responded to a course of corti‐ costeroids need to be investigated for chronic infectious endophthalmitis. One should al‐ ways consider the possibility of having an infection within the capsular sac with Propionibacterium species, Corynebacterium species, or coagulase negative Staphylococci. [1, 3, 23, 24] Such infections may persist years after the ocular surgery and require an anteri‐ or chamber and vitreous tap. Some of the bacterial organisms may be sequestered within macrophages surrounded by lens capsule. In these circumstances, removal of the intraocular lens or exchange to prevent recurrent or persistent endophthalmitis may be necessary. These patients may present initially as having uveitis and hypopyon within 6-8 weeks of surgery, which fails to respond to corticosteroids and needs eventual vitrectomy with intra-vitreal antibiotics and often the removal of the intraocular lens (IOL). In chronic saccular endoph‐ thalmitis, there is granulomatous inflammation and characteristic white capsular plaque. [13, 23] A"trial of therapy"with Clarithromycin or Azithromycin may be considered since these drugs penetrate well into the tissue, and Propionibacterium acnes is very sensitive to these drugs. [13, 24, 25] For unknown reasons, culture-negative endophthalmitis may re‐ spond well when the patient is treated with clarithromycin. [25] One needs to be aware, that Propionibacterium acnes may appear as a Gram-variable coccobacillus when the specimen is obtained from the anterior chamber or vitreous. The PCR technique has been found to be more sensitive to identify bacteria in these situations. [20] Molecular techniques using multi‐ plex or broad-range PCR may enable rapid detection and identification of causative patho‐ gens in ocular infectious diseases. In certain circumstances, PCR technique may provide the results of the causative micro-organism within 6 hours of biopsy. The PCR method offers much improved pathogen detection especially in the case of chronic endophthalmitis with low pathogen counts. PCR was extensively evaluated in the multi-center European prophy‐ laxis study of postoperative endophthalmitis following cataract surgery and was found to be useful in identifying 6 out of 20 pathogens causing endophthalmitis where standard Gram-stain and cultures results were found to be negative. [11] Multiplex PCR has the drawback of allowing only a limited number of genes to be analyzed in one reaction, and pre-identification of the species level is required. Analysis of amplicons by DNA sequencing after broad-range PCR, are the most used techniques for identifying DNA, but the time and effort associated with data analysis lead to some limitations. Therefore, improved highthroughput genotyping methods that are sensitive and discriminative may be desired. DNA microarray technology has been found to be a promising genotyping method that allows si‐ multaneous identification of a wide variety of genes and rapid determination of the genetic profile of a microorganism in a single experiment. DNA microarray technique may be useful for genetic screening and identification of microorganisms in cases of suspected infectious endophthalmitis. [26]

#### **4. Exogenous bacterial endophthalmitis**

from these patients for Gram staining, culture, and Polymerase Chain Reaction (PCR) assay. [20] Anterior chamber and vitreaous specimens obtained should be directly inoculated on to the culture media at the time of procedure. If any of these investigations yield a positive re‐ sult, the case can be classified as a proven case of infective endophthalmitis; otherwise the case should be classified as presumed unproven endophthalmitis. Each unproven case should be carefully considered if there is evidence of the Toxic Anterior Segment Syndrome (TASS) or non-infective uveitis when the case is not considered infective otherwise. [21, 22] Patients presenting late after surgery with uveitis that has not responded to a course of corti‐ costeroids need to be investigated for chronic infectious endophthalmitis. One should al‐ ways consider the possibility of having an infection within the capsular sac with Propionibacterium species, Corynebacterium species, or coagulase negative Staphylococci. [1, 3, 23, 24] Such infections may persist years after the ocular surgery and require an anteri‐ or chamber and vitreous tap. Some of the bacterial organisms may be sequestered within macrophages surrounded by lens capsule. In these circumstances, removal of the intraocular lens or exchange to prevent recurrent or persistent endophthalmitis may be necessary. These patients may present initially as having uveitis and hypopyon within 6-8 weeks of surgery, which fails to respond to corticosteroids and needs eventual vitrectomy with intra-vitreal antibiotics and often the removal of the intraocular lens (IOL). In chronic saccular endoph‐ thalmitis, there is granulomatous inflammation and characteristic white capsular plaque.

**Figure 3.** External photograph of a patient with history of cataract surgery who presented with severe conjunctivitis,

corneal opacification and vascularization was found to have evidence of endophthalmitis.

176 Common Eye Infections

Patients may present days or several weeks following cataract or other ocular surgery with re‐ duced visual acuity (VA) and signs of inflammation in the anterior chamber along with other evidence suggestive of endophthalmitis. [27, 28] Intraocular surgery remains the most com‐ mon cause of endophthalmitis considering the number of cataract surgeries being performed around the World. [12] The infection may also occur following glaucoma surgery, retina sur‐ gery and even following strabismus surgery. [29, 30] Ocular trauma remains another major source of endophthalmitis especially in cases of Retained Intraocular Foreign Body (IOFB). Symptoms of acute endophthalmitis in these patients may include decreased vision, pain, swollen eye lids, conjunctival chemosis with discharge and photophobia. [31] There may be signs of conjunctival and corneal edema, anterior chamber inflammation with inflammatory cells, hypopyon or fibrin clot (Figure 4). Presence of vitreous haze may prevent clear view of the fundus. Loss of the red reflex may be a poor guide to the general state of the vitreous, which may be most opaque anteriorly where the inflammatory process has begun. In some in‐ stances, signs of endophthalmits following ocular surgery or trauma may appear soon. For ex‐ ample, acute suppurative endophthalmitis due to Streptococcus pyogenes may occur days after cataract surgery in which case the patient may present with swollen eyelid, opaque cor‐ nea, conjunctival chemosis and significant pain. [2, 3] Endophthalmitis elicits an aggressive inflammatory reaction that can result in the breakdown of the blood-ocular barrier. Such acute inflammatory process may need to be controlled in order to preserve vision by protecting the uveal tissue. Intra-vitreal Dexamethasone at the time of vitreal biopsy and intra-vitreal antibi‐ otics has been found to be very helpful in minimizing uveal tissue damage.

**Figure 4.** External photograph of a patient's right eye who presented with decreased vision, pain, tearing, redness and photophobia several days after having penetrating trauma to his right eye. He was found to have conjunctival chemosis along with anterior chamber hypopyon (a). Ultrasonography revealed evidence of vitreous opacification suggestive of endophthalmitis (b).
