Endophthalmitis: Clinical Guidelines

List of Abbreviations

AB – antibiotic

IOP – intraocular pressure

IAC – intracameral administration

CS – corticosteroids

ONH – optic nerve head

IOL – intraocular lens

CT – clinical trial

ICD-10 – International Classification of Diseases, 10th Revision

NSAIDs – nonsteroidal anti-inflammatory drugs

PFC – perfluorocarbon

SO – silicone oil

vitreous body

US – ultrasound examination

EIR – exudative-inflammatory reaction

EFP – electrophysiological tests

FCM – flare cell photometry

Terms and Definitions

Acute postoperative endophthalmitis — an infectious inflammatory disease of the internal membranes of the eye occurring after surgical intervention, in most cases on days 2–7, and manifesting as an acute course with exudation into the anterior and posterior chambers, vitreous body, and vitreous cavity.

Chronic postoperative endophthalmitis is an infectious inflammation of the internal membranes of the eye developing 4 or more weeks after surgery, manifesting with an indolent, relapsing course with exudation into the anterior and posterior chambers of the eye, vitreous body, and vitreous cavity.

Post-traumatic endophthalmitis is an acute infectious inflammatory disease of the internal membranes of the eye resulting from contamination by a mixed infection from a wounding agent, manifesting with exudation into the anterior and posterior chambers of the eye, vitreous body, and vitreous cavity.

Panophthalmitis is a complicated course of endophthalmitis characterized by generalization of the inflammatory process with involvement of all membranes of the eye and orbital tissues.

TASS (Toxic Anterior Segment Syndrome) is aseptic postoperative inflammation localized in the anterior segment of the eye.

TPSS (Toxic Posterior Segment Syndrome) is aseptic postoperative inflammation localized in the posterior segment of the eye.

Exudative-inflammatory reaction of the eye (exudative iritis, iridocyclitis, postoperative uveitis, "sterile" endophthalmitis) is aseptic postoperative inflammation characterized by involvement of and exudation in the posterior segment of the eye, frequently accompanied by combined inflammation of the posterior and anterior segments of the eye.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Endophthalmitis is an infectious purulent-inflammatory disease of the internal membranes of the eye resulting from bacterial or fungal contamination during or immediately after surgery/trauma, less commonly from the spread of infection from endogenous sources, with exudation into the anterior and posterior chambers of the eye, vitreous body, and vitreous cavity [1-5].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Acute postoperative endophthalmitis

In most cases, postoperative endophthalmitis is caused by the patient's own microflora of the ocular surface and periocular skin [6]. Contamination by exogenous microflora on the surface of medical instruments, irrigation solutions, IOLs, injectors, and medical personnel's hands is extremely rare. Infection can occur due to microorganisms penetrating inside the eyeball through the incision during the procedure, or afterward if the hermetic seal of the surgical accesses is compromised. Subsequently, if the anatomical barrier between the anterior and posterior segments of the eyeball is disrupted via defects in the posterior lens capsule, zonular apparatus, and anterior hyaloid membrane, microorganisms easily contaminate the vitreous body, which serves as an excellent nutrient medium for them [7, 8]. There they multiply and produce various pathogenicity factors (toxins) that trigger the inflammatory process.

Risk factors for acute endophthalmitis associated with the eyeball and its adnexa include: anatomical features of the palpebral fissure structure (deep-set eyeball), eyelid malpositioning which can cause accumulation of irrigation fluid on the ocular surface and increase the risk of bacterial contamination; inflammatory diseases of the ocular surface in the form of chronic conjunctivitis, blepharitis, canaliculitis, obstruction of the lacrimal pathways at the level of the lacrimal sac isthmus and nasolacrimal duct; wearing soft contact lenses, presence of a cosmetic prosthesis in the contralateral orbit [1, 3, 9-13].

Intraoperative risk factors include the placement of an eyelid speculum, following which there is an increase in microbial load due to the compression of the meibomian gland ducts and the evacuation of their secretion into the conjunctival sac [7].

The causative agents of endophthalmitis are bacteria and fungi, distributed by frequency of occurrence as follows [1, 4, 5, 14-18]:

1. Staphylococci:

• 33 – 77% — Staphylococcus epidermidis and other species of coagulase-negative staphylococci (CoNS),

• 10 – 21% — Staphylococcus aureus.

2. Streptococci:

• 9 – 19% — β-hemolytic streptococcus, including (Streptococcus mitis and Streptococcus salivarius), pneumococcus (Streptococcus pneumoniae),

  2 – 10% — other gram-positive cocci, including enterococci (Enterococcus faecalis, Enterococcus faecium, Enterococcus casseliflavus) [19-23].

3. Gram-negative bacteria:

• 6 – 22% — Pseudomonas aeruginosa, including (Stenotrophomonas maltophilia, Burkholderia cepacia complex and other species).

4. Fungi:

• up to 8% — Candida spp., Aspergillus spp., Fusarium spp.

The isolation rate of major pathogens of postoperative endophthalmitis is comparable in European and North American countries, as confirmed by large-scale studies: the EVS study (Results of the Endophthalmitis Vitrectomy Study. A randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis, USA, 1996) [24], the ESCRS study (ESCRS guidelines for prevention and treatment of endophthalmitis following cataract surgery, 2007), and the Swedish National Study (Sweden, 2013). The species composition of endophthalmitis pathogens in the Asian region differs significantly. In particular, the proportion of endophthalmitis caused by gram-negative bacteria and fungi is significantly higher than in Europe and America. In China, the proportion of gram-negative bacteria in endophthalmitis reaches 26.2%, and fungi 16.7%; in India, 13.4% and 12.7%, respectively [5, 14-16]. The ocular surface microbiota may vary depending on the host's ethnicity, and change as a result of environmental influences and other causes [25, 26].

According to classical concepts, the clinical picture of an acute infectious inflammatory process in endophthalmitis develops by 2 to 7 days after surgery, which is associated with the pathogenesis of this complication, which generally goes through 3 stages of the infectious process: the incubation phase, the phase of accelerated bacterial growth, and the phase of bacterial cell death. During the incubation period, an increase in the number of microorganisms to a critical value is observed; the duration of this phase is at least 16–18 hours. Next, fibrin exudation and cellular infiltration by neutrophilic granulocytes occur. The severity of clinical manifestations in the anterior chamber of the eye depends on the virulence of the bacteria, the toxins they release, and the state of the patient's immune system. Clinical signs of inflammation appear in the anterior segment and posterior chamber of the eye on days 2 to 4 after surgery, after which the inflammatory process involves the vitreous body. The accumulation of exudate in the posterior segment of the eye occurs quite rapidly due to the low natural drainage capacity of the vitreous body. Frequently, exudate with bacteria fills the entire vitreous cavity, a fibrin clot forms, causing the development of both anterior and posterior proliferative vitreoretinopathy, and the inflammatory process transitions from the phase of accelerated bacterial growth to the phase of their cell death. Special attention should be paid to patients with aphakia/avitria, since the transition from one phase of the pathological process to another proceeds significantly faster in them due to the rapid migration and accumulation of the pathogen in the vitreous cavity fluid [5].

An important link in the pathogenesis of the disease is the involvement of the retina in the inflammatory process, leading to the destruction of the photoreceptor apparatus. Damage to the internal membranes occurs due to inflammatory mediators (histamine, serotonin, hydroperoxides, hydroradicals, bradykinins, prostaglandins, and others), and is also caused by the accumulation of bacterial metabolic products (exotoxins and proteases). In addition to the bacterial components themselves, which can act as antigen-presenting cells, the severity of the inflammatory course is determined by bacterial toxins that have a tropism for target tissues and exert a destructive effect on them. Involvement of the outer layers of the retina in the inflammatory process minimizes the likelihood of restoring visual functions as an outcome of treatment [5, 24, 27-32].

In a number of cases, bacterial contamination of the filtering bleb may occur after anti-glaucoma surgery, especially when using antineoplastic/cytostatic drugs, with the subsequent development of blebitis 4 or more weeks after surgery, which proceeds acutely with the threat of both functional and anatomical loss of the eye [5].

Chronic postoperative endophthalmitis

Chronic postoperative endophthalmitis develops 4 or more weeks after surgery and is characterized by an indolent, recurrent course. The causative agents of this disease are most often propionibacteria (Propionibacterium acnes), and less frequently Staphylococcus epidermidis, actinomycetes (Actinomyces israelii), and corynebacteria (Corynebacterium spp.). A specific feature of this complication is the entry of a small amount of low-virulence bacteria into the capsular bag and their subsequent isolation due to adhesion of the anterior and posterior lens capsule, known as "intracapsular" chronic postoperative endophthalmitis [1, 5, 33, 34].

Post-traumatic endophthalmitis

Post-traumatic endophthalmitis is typically characterized by mixed infection contamination, directly depending on the nature of the injury and the level of contamination of the traumatic agent [1, 35-37]. The stages of development of this type of endophthalmitis are similar to those of acute postoperative endophthalmitis [35].

Microorganisms penetrate the eyeball cavity either directly at the time of the wound (primary microbial invasion) or some time after the trauma (secondary microbial invasion). While in the first case the clinical picture usually develops within the first 2-3 days after a penetrating eye injury, in the second case clinical signs may appear at a later date. Secondary microbial exogenous invasion is facilitated by inadequate adaptation of crushed wound edges, the formation of a filtering scar, etc. [35-39].

Fungal endophthalmitis

Fungal endophthalmitis is a relatively rare, extremely formidable vision-threatening condition with an extremely variable clinical presentation, complex diagnosis, individual treatment algorithm, and doubtful functional and anatomical prognosis, capable of leading to the loss of the eye as an organ in the shortest possible time. The causative agents of fungal endophthalmitis are most often yeasts (Candida spp., Malassezia spp., Microsporum spp., etc.) and molds (Aspergillus spp., Cephalosporium spp., Mucor spp., Fusarium spp., Paecilomyces spp., etc.) [40]. Fungi penetrate the eye cavity via endogenous and exogenous routes, just like bacterial infection.

The main risk factors for the development of endogenous fungal endophthalmitis include pronounced immunosuppression, AIDS, granulocytopenia, intravenous drug abuse, long-term indwelling catheters, bacterial sepsis in hospitalized patients, systemic antibiotic use, intensive corticosteroid therapy, the early postoperative period after major surgery (especially involving the gastrointestinal tract and urological system), malignancies, alcoholism, diabetes mellitus, polytrauma, hemodialysis, the postpartum period, prematurity, and organ transplantation [41-44]. In the presence of fungemia, endogenous spread of the infection typically occurs, leading to the development of so-called hematogenous dissemination of systemic fungal infection.

The cause of exogenous fungal endophthalmitis is damage to the corneal stroma with the entry and proliferation of fungi on its surface; the process frequently ends in the destruction of Descemet's membrane, with keratouveitis progressing to fungal endophthalmitis. Vehicles of fungal infection, particularly Fusarium, can include contact lenses, cases, and storage solutions [45]. Fungal infection can also enter from the outside during major surgical interventions; in such cases, contamination is associated with intraoperative introduction of fungal spores into the eye cavity, though the incidence of infection via this route is extremely low [46-51].

1.3 Epidemiology of the Disease or Condition

Acute postoperative endophthalmitis

Currently, thanks to advances in surgical technology—including the transition from intracapsular cataract extraction to small-incision surgery using ultrasound energy, the emergence of new classes of antibacterial drugs, and the improvement of anti-epidemic measures for the prevention of nosocomial infections—the risk of postoperative complications is significantly reduced. Thus, according to the ESCRS study (2007), the incidence of postoperative endophthalmitis after phacoemulsification in patients who did not receive intracameral #cefuroxime** injection and levofloxacin** eye drops was 0.35%, while with the intracameral use of #cefuroxime**, the incidence of endophthalmitis decreased to 0.05% [1, 5, 16].

Results of retrospective studies conducted in the USA, Poland, South Korea, and China showed that the incidence of endophthalmitis after phacoemulsification ranged from 0.04% to 0.06%. In a multicenter randomized clinical trial organized by the European Society of Cataract and Refractive Surgeons (ESCRS, 2013), it was established that the incidence of acute endophthalmitis varies significantly (0.025% – 0.226%) depending on the specific use of antiseptics and antibiotics in perioperative prophylaxis (Table 1) [10, 52-60].

In Russia, this figure does not exceed 0.1%; specifically, within the structure of the S.N. Fyodorov Eye Microsurgery Federal State Institution of the Russian Ministry of Health, the incidence of endophthalmitis after cataract surgery ranges from 0.03 to 0.07% [61-66].

The incidence of endophthalmitis after 23G and 25G micro-invasive vitrectomy reaches 0.14% in Sweden and 0.052% in India; after glaucoma surgery, it occurs in 0.00074–0.00197% of cases in the Kingdom of Saudi Arabia and in 0.06–0.2% of cases in France. An analysis of complications from 15,000 injections of various anti-VEGF drugs performed in the USA established that the probability of developing endophthalmitis is 0.2% [1, 5, 28].

Table 1. Incidence of acute endophthalmitis depending on the perioperative prophylaxis algorithm according to the results of certain clinical trials [10]

Chronic postoperative endophthalmitis

The incidence of this complication is 0.02 – 0.05% [1, 5, 33, 34].

Post-traumatic endophthalmitis

The incidence of endophthalmitis after penetrating injuries of the eyeball reaches 5 – 25%. In agricultural eye injuries, the infection rate reaches 25 – 50% [1, 35-37].

Fungal endophthalmitis

As recently as the middle of the last century, fungal endophthalmitis was considered an "exotic" condition. Currently, its incidence has increased almost 50-fold, reaching from 6.2 to 16.7% in the structure of intraocular infections [46, 51, 67, 68].

1.4 Features of Coding the Disease or Condition

H44.0 — Purulent endophthalmitis

H44.1 — Other endophthalmitis

1.5 Classification of the disease or condition

There is no generally accepted clinical classification of endophthalmitis approved by all-Russian public organizations such as the "Society of Ophthalmologists of Russia" or the "Association of Ophthalmologists".

In 2019, specialists from the Cheboksary Branch of the S.N. Fyodorov Eye Microsurgery Federal State Institution of the Russian Ministry of Health proposed a clinical classification of acute postoperative endophthalmitis based on the severity of the inflammatory process (determined subjectively and objectively using laser flare photometry) and taking into account changes in electroretinography (ERG) parameters [28] (Table 2).

Acute endophthalmitis can be exogenous (postoperative, post-traumatic, post-injection) due to contamination of the surgical wound, instruments, equipment, and intraocular lenses with resident microflora from the ocular surface, or the entry of foreign bodies (particles) into the eye, as well as endogenous (septicemia) [1, 4, 5, 69-71].

Depending on the severity of the disease, endophthalmitis can be conditionally divided into mild, moderate, severe, extremely severe grades, and panophthalmitis. The severity of the disease depends on the virulence of the infecting pathogen (including bacterial load, replicative capacity, and toxin production), as well as on the patient's immune response (inflammatory mediators and subsequent tissue necrosis) [72, 73]. Endophthalmitis caused by streptococci is particularly severe due to specific virulence factors and is frequently associated with an unfavorable visual prognosis even with timely and comprehensive antibiotic therapy [74].

In mild endophthalmitis, the patient retains form vision; cellular suspension in the anterior chamber (which does not impede visualization of the iris and lens) or a small (up to 0.5 mm) hypopyon appears; vitreous floaters are present with a preserved red reflex and the possibility of ophthalmoscopy of large details of the ocular fundus. Visual functions may remain high [1, 5, 35, 75].

In moderate endophthalmitis, the infectious inflammatory process caused by the least virulent microorganisms tends to have a later clinical manifestation. Such endophthalmitis is characterized by mild pain syndrome, absent or small (0.5–2 mm) hypopyon, vitreous floaters, iris bombe, absence of pupillary light reflex, retinal periphlebitis with a preserved fundus reflex and the possibility of partial ophthalmoscopy of large details of the ocular fundus, and a decrease in visual functions down to finger counting from 30 centimeters or hand motion recognition at a distance from the face [1, 4, 5, 35, 75].

Severe endophthalmitis is characterized by pronounced manifestations of the infectious process, accompanied by pain syndrome, fibrinous exudate precipitation in the anterior chamber, hypopyon (2 mm or more), iris bombe, absence of pupillary light reflex, a fibrinous clot in the posterior chamber and vitreous cavity, absence of fundus reflex and impossibility of ophthalmoscopy, and a significant decrease in visual functions down to light perception with accurate or inaccurate light projection [1, 3-5, 9, 30, 35, 64-66].

Extremely severe endophthalmitis manifests with a corresponding degree of infectious inflammation, accompanied by pain, eyelid edema, chemosis, purulent discharge from the conjunctival cavity, corneal infiltration, pronounced hypopyon (2 mm or more), iris bombe, massive exudation into the anterior chamber, vitreous body, and vitreous cavity, and is also characterized by a drastic decrease in visual functions down to inaccurate light projection or no light perception [1, 3-5, 9, 30, 35, 64-66].

Panophthalmitis is a complicated form of endophthalmitis characterized by the generalization of the inflammatory process with purulent melting of the ocular tunics and a pronounced reaction of orbital tissues, accompanied by exophthalmos, impaired mobility of the eyeball, and pain syndrome. The clinical course is typically rapidly progressive and aggressive, ending in the loss of the eye, which may require its evisceration [35, 36].

Table 2. Classification of acute postoperative endophthalmitis. Frolychev I.A., Pozdeeva N.A. (2019)

Endophthalmitis is classified by the type of exudation in the vitreous cavity [35, 36]:

1. focal,

2. diffuse,

3. mixed

1.6 Clinical presentation of the disease or condition

Acute postoperative endophthalmitis

The clinical presentation of acute postoperative endophthalmitis is characterized by a rapid increase in intraocular inflammation. On days 2–7 (in rare cases up to 6 weeks) after surgery, blurred vision, pain syndrome, and eye redness appear. Examination of the eyeball reveals hypopyon, fibrin or precipitates on the IOL and corneal endothelium, edema, iris bombe, irregular pupil shape, absence of its reaction to light, the fundus reflex becomes gray or yellow due to vitritis and the formation of exudate in the posterior chamber, vitreous body, and vitreous cavity. Vitritis is confirmed by ocular ultrasound—B-scan ultrasonography, which reveals thickening of the choroid and pronounced cellular infiltration of the vitreous body. Based on clinical data and instrumental studies, a clinical diagnosis of "acute postoperative endophthalmitis" is established [1, 3-5, 30-32, 35, 36, 61-66, 69, 71].

Chronic postoperative endophthalmitis

The initial signs of this complication appear with a delay (starting from the second month of the postoperative period). Chronic endophthalmitis is characterized by mild anterior uveitis, sometimes with large "mutton-fat" keratic precipitates. Vitreous floaters are more frequently detected, and hypopyon is less common. A distinguishing feature of chronic endophthalmitis is the presence of progressive whitish opacities of the lens capsule, characteristic of Propionibacterium acnes, with subsequent accumulation of the pathogen in the capsular bag fornices. Treatment of chronic endophthalmitis is complicated by the fact that bacteria are isolated from the action of antibacterial drugs [33, 34].

Periods of exacerbation alternate with remission against the background of intensive conservative antibacterial and steroid anti-inflammatory therapy [33, 34].

Post-traumatic endophthalmitis

The clinical presentation of post-traumatic endophthalmitis is similar to acute postoperative endophthalmitis. Given that contamination is caused by a penetrating wound, manifestations of endophthalmitis are often combined with other trauma symptoms: corneal wound, cataract, hemophthalmus, choroidal detachment, retinal detachment, etc. [1, 35-37].

Fungal endophthalmitis

In the early stages of fungal endophthalmitis, the inflammatory process proceeds without pronounced specific signs. The main complaint is decreased vision without pain syndrome [46, 51]. The clinical presentation of fungal endophthalmitis varies in both endogenous and exogenous forms; the onset of the disease is usually subacute, and both eyes may be affected. Examination reveals eyelid edema, conjunctival injection, opalescence and cellular suspension in the aqueous humor with or without hypopyon, absence of red reflex, and exudation into the vitreous body [6]. The duration of endogenous endophthalmitis may differ from that of exogenous endophthalmitis; the latent periods of clinical manifestations in postoperative and post-traumatic fungal endophthalmitis average 20 and 7 days, respectively, whereas in endogenous fungal endophthalmitis, the average latent period is 30 days. Corneal edema is more common in exogenous fungal endophthalmitis (postoperative (18.9%) and post-traumatic (22.9%)) compared to endogenous (8.3%). Hypopyon is more typical for exogenous (postoperative (64.5%) and post-traumatic (62.5%)) compared to endogenous (25.0%). The formation of vitreous exudate without a red reflex is equally characteristic of endogenous fungal endophthalmitis (50%) and postoperative fungal endophthalmitis (58.5%), and is more characteristic of post-traumatic fungal endophthalmitis (85.4%) [70].

Post-traumatic fungal endophthalmitis manifests with purulent exudate, eyelid edema, chemosis, corneal edema or hypopyon, vitritis, retinitis with a slowly progressive course and periods of temporary improvement [76-78].

Aspergillary endophthalmitis generally has a more severe course compared to candidal endophthalmitis, with more extensive areas of retinal necrosis and retinal hemorrhages. In endogenous fungal endophthalmitis caused by Aspergillus, invasion of the pathogen into the walls of retinal and choroidal blood vessels occurs, in contrast to the invasion of Candida into the vitreous body [42, 77, 78]. Therefore, in aspergillary endophthalmitis, retinal vein occlusion with focal hemorrhages, exudate, and retinal necrosis may be observed. These clinical manifestations are less characteristic of endophthalmitis caused by Candida.

All intraocular inflammation following surgical treatment must be divided into 2 types: aseptic and septic. Aseptic (non-infectious) inflammation includes toxic anterior segment syndrome (TASS) and toxic posterior segment syndrome (TPSS) [79-84]. In 1992, S.N. Fedorov and E.V. Egorova proposed a general term for aseptic intraocular inflammation—exudative-inflammatory reaction of the eye. There are 4 degrees of this type of inflammation: Grade 1 (areactive course)—fine cell suspension in the aqueous humor, isolated folds of Descemet's membrane; Grade 2—postoperative iritis with corneal edema and desçemétite around the surgical wound, punctate suspension in the aqueous humor, vitreous opacity; Grade 3—iridocyclitis with total corneal edema and desçemétite, dense suspension in the aqueous humor, loose exudate in the pupil area and on the IOL surface, mild exudation in the vitreous cavity; Grade 4—postoperative endophthalmitis with marked exudation in the vitreous cavity [85, 86]. The degrees of inflammation also serve as the stages of the disease. A special type of non-infectious inflammation is delayed-onset retinovasculitis. This complication may occur after intravitreal injection of certain angiogenesis inhibitors [87-89].

Septic (infectious) inflammation includes acute early infectious endophthalmitis, acute late infectious endophthalmitis, and chronic infectious endophthalmitis.

Differential diagnosis of these complications is extremely important due to different treatment approaches [1, 2-5, 7, 30-32, 35, 36, 61-66, 79-89].

Differential diagnosis of postoperative inflammation is presented in Table 3 (see subsection 2.5.2).

2. Diagnostics, medical indications and contraindications for diagnostic methods

The diagnosis of endophthalmitis is established based on:

- complaints (sharp decrease in vision, eye pain, eye redness);

- anamnesis (prior surgical intervention or penetrating injury, or presence of chronic infection foci in the body);

- biomicroscopy of the eye and ophthalmoscopy (cell suspension in the anterior chamber and vitreous cavity, hypopyon, exudation in the vitreous cavity);

- ultrasound examination of the eyeball (presence of exudate in the vitreous cavity).

Any inflammation following penetrating injuries is considered infectious by default with a high risk of developing endophthalmitis [1, 35-37].

2.1 Complaints and Anamnesis

Comments:

Postoperative endophthalmitis

Anamnestic data collection includes assessing the duration and rate of visual acuity decrease, progression of disease symptoms, subjective assessment of the pain syndrome, general health status, pre-hospital treatment administered, and prior surgery performed.

Post-traumatic endophthalmitis

When taking the anamnesis, it is necessary to clarify the circumstances of the trauma and determine the properties of the damaging agent (including its trajectory). It is necessary to detail the scope of previous surgical interventions, as well as the type and frequency of therapy used at the time of examination.

2.2 Physical Examination

2.3 Laboratory Diagnostics

When conducting laboratory diagnostics for endophthalmitis, interaction between the ophthalmology clinic and the microbiological laboratory is necessary.

Comments: conjunctival and corneal cultures are advisable if endophthalmitis is a complication of keratitis or develops from bleb inflammation. Material for culture is collected from the inner surface of the lower eyelid using two or three circular motions from the lateral to the medial corner of the palpebral fissure. After material collection, the swab/microbiological loop is immersed in a tube with transport medium and sent to the bacteriological laboratory.

The study results are used to adjust antibacterial or antifungal therapy.

Comments: material collection is performed prior to surgical treatment after biomaterial collection, samples are immersed in a tube with transport medium and sent to the microbiological laboratory for traditional (culture) examination for aerobic and facultatively anaerobic microorganisms, and determination of microbial susceptibility to antimicrobial chemotherapeutic agents.

Comments: after biomaterial collection, samples are immersed in a tube with transport medium and sent to the microbiological laboratory for traditional (culture) examination for fungi.

2.4 Instrumental Diagnostics

Comments: visual acuity testing is performed by a physician; a decrease in vision with best correction down to counting fingers at face distance indicates the need for emergency surgery; a decrease in vision to pr.l. incerta is prognostically unfavorable in terms of visual function recovery; when vision drops to 0 (zero), surgical treatment is performed with globe-preserving intent.

Comments: subjective tyndallometry with determination of opalescence and the severity of exudation in the anterior chamber is mandatory (mild—1+; moderate, iris and lens details clearly visible—2+; marked, iris and lens details visible through a haze—3+; intense, anterior chamber filled with fibrinous exudate—4+. Assessment of the degree of vitreous opacity is also mandatory: +0.5—slight blurring of the optic disc margins and/or loss of the nerve fiber layer light reflex; +1.0—slight blurring of retinal vessels and the optic nerve; +1.5—blurring of the optic disc and retina in the posterior pole greater than at +1.0, but less than at +2.0; +2.0—moderate blurring of the optic disc, +3—marked blurring of the optic disc; +4—optic disc is not visible. In cases of marked exudation and cell suspension in the anterior chamber and/or vitreous body, ophthalmoscopy is difficult; in such cases, the color of the fundus reflex (pink/gray/yellow) is assessed. Weakening and/or loss of the fundus reflex is a clinical sign indicating the need for immediate vitrectomy.

Comments: to measure intraocular pressure, Maklakov tonometry is performed; pneumotonometry (used when discharge is present in the conjunctival cavity, which interferes with contact methods); tonometry using I-Care type tonometers, and Goldmann tonometry. Normally, the IOP difference should not exceed 2 mm Hg. If hypotony is present in endophthalmitis (even minor), penetrating eye injury, cyclodialysis, and retinal detachment must be ruled out.

Comments: if there is formal vision, the visual field boundaries are assessed by a standard method using a perimeter. Visual field losses or significant constrictions may indicate the formation of exudate in the vitreous cavity, retinal detachment, and toxic retinal damage.

Comments: the main methods are two-dimensional (B-scan) or one-dimensional (A-scan) echography (B-scan is the preferred method), during the study it is important to determine the presence or absence of posterior vitreous detachment and retinal detachment.

2.5 Other Procedures

2.5.1 Additional diagnostic tests and studies

Comments: the decision to prescribe other additional diagnostic methods (determining the electrical sensitivity threshold and optic nerve lability, performing electroretinography, electrooculography) is made by the physician based on the results of the baseline examination; deviation from normal values will indicate toxic damage to the retina.

Comments: the method allows determining the degree of blood-ocular barrier damage and quantitatively assessing the inflammatory reaction of the eye (normally, average protein flare values are 4.56 ± 1.8 ph/ms). In mild endophthalmitis, this value corresponds to 25–79 ph/ms, moderate to 80–149, severe to 150 and above, and extremely severe to unmeasurable.

2.5.2 Differential diagnosis of postoperative inflammation

Table 3. Differential diagnosis of postoperative inflammation [1, 2-5, 7, 30-32, 35, 36, 61-66, 79-89]

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1 Conservative Treatment

Conservative treatment is used only in combination with surgery. Conservative treatment is initiated immediately upon identifying the first symptoms of endophthalmitis.

Comments: local antibacterial and anti-inflammatory treatment is performed before and after the surgical stage (intravitreal antibiotic injection / vitrectomy) and aims to maintain the minimum inhibitory concentration (MIC) of antibiotics in the anterior chamber and vitreous cavity while providing an anti-inflammatory effect. Mydriatics are used to dilate the pupil to prevent posterior synechiae formation and reduce ocular inflammation.

Comments: Antibiotics are administered in separate syringes. The combined use of #vancomycin** and #ceftazidime** covers the broadest spectrum of potential endophthalmitis causative agents: #vancomycin** has a bactericidal effect against Gram-positive microflora, and #ceftazidime** against Gram-negative microflora. In case of individual intolerance to #vancomycin** and #ceftazidime** and/or identification of microflora resistant to these antibiotics, alternative optimal antibiotics may be selected individually.

Comments: if endophthalmitis is the probable diagnosis, treatment is initiated with the conservative therapy outlined above; if no positive dynamics are observed within 24 hours, surgical treatment in the form of subtotal vitrectomy must be initiated.

Comments: clarithromycin is an erythromycin derivative that is well absorbed from the gastrointestinal tract and penetrates into the eye. It is effective against Gram-positive and many atypical bacteria.

Local drug therapy is similar to postoperative prescriptions for acute endophthalmitis management described above. If conservative therapy yields no positive dynamics, conversion to surgical treatment is necessary.

3.2 Surgical Treatment

Acute endophthalmitis

Comments: intravitreal antibiotic injection as monotherapy is performed in patients with mild endophthalmitis and in other cases: in the absence of necessary equipment or a vitreoretinal surgeon with appropriate expertise. If no positive dynamics are observed 24 hours after the initiation of treatment (intravitreal antibiotic injection), the patient must be urgently referred to a clinic capable of performing a vitrectomy.

Comments: vitrectomy should be performed within 24 – 48 hours from the onset of the first signs of endophthalmitis; prior to vitrectomy, sampling of material from the anterior chamber and vitreous cavity is mandatory to identify microorganisms and determine their antibiotic susceptibility [1, 5, 100, 110]. Findings supporting the diagnosis of endophthalmitis include intraoperative findings such as exudate in the vitreous cavity, intraretinal hemorrhages, epiretinal exudate or epiretinal membranes (beneath the posterior hyaloid), paravascular "cuffs", and retinal edema along the vascular arcades.

Comments: at the end of the procedure, the vitreous cavity is filled with PFCL, and antibiotics are administered intravitreally. The duration of tamponade is 5 – 14 days. As the inflammatory process subsides, the transparency of the optical media is restored, and the second stage of surgery is performed – removal of the PFCL or replacement of the PFCL with silicone oil.

Treatment of chronic endophthalmitis

Treatment of fungal endophthalmitis

The treatment of fungal endophthalmitis follows the same principles used in the management of acute postoperative bacterial endophthalmitis: standard posterior closed subtotal vitrectomy (A16.26.089.002), invariably supplemented by intravitreal and systemic administration of antifungal agents.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

5. Prevention and Dispensary Observation

6. Organization of Medical Care

1. Outpatient ophthalmologist: initial examination, disease detection, diagnosis establishment, emergency referral to a 24-hour inpatient facility (including by ambulance transport) to provide specialized (including high-tech) medical care upon detecting signs of endophthalmitis.

2. In the ophthalmology inpatient unit: examination by an ophthalmologist, vitreoretinal surgeon (if available), history taking, diagnostics, instrumental and laboratory diagnostics, completion of medical documentation.

3. Surgery in a 24-hour inpatient setting, postoperative aftercare, ultrasound monitoring, attending physician follow-up.

4. Discharge for outpatient aftercare in case of satisfactory patient condition and no need for continued inpatient stay: scheduling follow-up examinations, issuing medical documentation with recommendations, and issuing a sick leave certificate upon request.

7. Additional Information

The outcome of the disease depends on the patient's timely seeking medical attention, the type and virulence of the microorganisms, and the promptness of surgical care.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Astakhov Sergey Yurievich – D.Sc. in Medicine, Professor, Head of the Department of Ophthalmology with the Prof. Yu.S. Astakhov Clinic at the Pavlov First Saint Petersburg State Medical University of the Russian Ministry of Health, Chief Freelance Ophthalmologist of the Northwestern Federal District, Vice-President of the All-Russian Public Organization «Association of Ophthalmologists»;

2. Zabolotniy Alexander Grigorievich – Ph.D. in Medicine, Associate Professor, Chief Researcher at the Krasnodar Branch of the S.N. Fyodorov Eye Microsurgery Federal State Institution of the Russian Ministry of Health, Head of Studies, Associate Professor of the Department of Eye Diseases at the Kuban State Medical University, Member of the All-Russian Public Organization «Russian Ophthalmological Society»;

3. Ilyukhin Pavel Andreevich – Ph.D. in Medicine, Head of the Department of Traumatology and Reconstructive Surgery at the Helmholtz National Medical Research Center of Eye Diseases of the Russian Ministry of Health, Leading Researcher, Highest Qualification Category Ophthalmologist, Member of the All-Russian Public Organization «Association of Ophthalmologists»;

4. Kazaikin Viktor Nikolaevich – D.Sc. in Medicine, Leading Researcher at the Ekaterinburg Eye Microsurgery Center JSC, Member of the All-Russian Public Organization «Russian Ophthalmological Society».

5. Kulikov Alexey Nikolaevich – D.Sc. in Medicine, Professor, Chief Ophthalmologist of the Russian Ministry of Defense, Head of the Department of Ophthalmology at the S.M. Kirov Military Medical Academy of the Russian Ministry of Defense, Member of the All-Russian Public Organization «Russian Ophthalmological Society»;

6. Nikolaenko Vadim Petrovich – Doctor of Medical Sciences, Deputy Chief Medical Officer for Ophthalmology at City Multidisciplinary Hospital No. 2 of Saint Petersburg, Professor at the Department of Otorhinolaryngology and Ophthalmology of Saint Petersburg University, member of the all-Russian public organization "Association of Ophthalmologists";

7. Morozova Tatiana Anatolyevna – Candidate of Medical Sciences, Head of the Diagnostic and Treatment Department (Nizhny Novgorod) of the Cheboksary Branch of the S.N. Fedorov National Medical Research Center "MNTK "Eye Microsurgery" of the Russian Ministry of Health, member of the all-Russian public organization "Society of Ophthalmologists of Russia";

8. Okolov Igor Nikolaevich – Candidate of Medical Sciences, Member of the Expert Council on Red Eye, member of the all-Russian public organization "Society of Ophthalmologists of Russia";

9. Pozdeeva Nadezhda Alexandrovna – Doctor of Medical Sciences, Professor, Director of the Cheboksary Branch of the S.N. Fedorov National Medical Research Center "MNTK "Eye Microsurgery" of the Russian Ministry of Health, member of the all-Russian public organization "Society of Ophthalmologists of Russia";

10. Ponomarev Vyacheslav Olegovich – Doctor of Medical Sciences, Deputy General Director for Scientific and Clinical Work at the Ekaterinburg Center of MNTK "Eye Microsurgery" JSC, member of the all-Russian public organization "Society of Ophthalmologists of Russia";

11. Plakhotniy Mikhail Alekseevich – Candidate of Medical Sciences, Head of the Operating Theatre at the Kaluga Branch of the S.N. Fedorov National Medical Research Center "MNTK "Eye Microsurgery" of the Russian Ministry of Health, member of the all-Russian public organization "Society of Ophthalmologists of Russia";

12. Soboleva Maria Alexandrovna – Ophthalmologist at the Helmholtz National Medical Research Center of Eye Diseases of the Russian Ministry of Health, member of the all-Russian public organization "Association of Ophthalmologists";

13. Frolychev Ivan Alexandrovich – Candidate of Medical Sciences, Deputy Director for Medical Work at the Cheboksary Branch of the S.N. Fedorov National Medical Research Center "MNTK "Eye Microsurgery" of the Russian Ministry of Health, member of the all-Russian public organization "Society of Ophthalmologists of Russia";

14. Chentsova Ekaterina Valerianovna – Doctor of Medical Sciences, Professor, Highest Qualification Category Ophthalmologist at the Department of Traumatology and Reconstructive Surgery of the Helmholtz National Medical Research Center of Eye Diseases of the Russian Ministry of Health, member of the all-Russian public organization "Association of Ophthalmologists".

Conflict of interest none declared.

Appendix A2. Methodology for Developing Clinical Guidelines

The methodology for developing clinical guidelines is based on evidence-based medicine methods.

Methods used for evidence collection/selection: electronic database searches; analysis of current scientific developments on glaucoma in Russia and abroad; synthesis of practical experience of Russian and foreign colleagues.

The preliminary version of these guidelines was reviewed by independent experts who commented on the accessibility and interpretability of the evidence underlying the guidelines for practitioners and patients.

The comments received from experts were carefully systematized and discussed by the chair and members of the working group. Each point was discussed, and appropriate changes were made to the guidelines.

In these clinical guidelines, all data are ranked by level of reliability (evidence) depending on the quantity and quality of studies on the issue.

Target audience of these clinical guidelines:

1. Ophthalmologists;

2. General practitioners (family physicians).

Table 1. Levels of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)

Table 2. Levels of Evidence (LoE) grading scale for prevention, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitation interventions)

Table 3. Scale for grading levels of clinical persuasiveness of recommendations (LCPR) for prevention, diagnostic, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The clinical guidelines update mechanism provides for their systematic revision—at least once every three years, as well as upon the emergence of new evidence-based data regarding the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

These clinical guidelines were developed taking into account the following regulatory legal documents:

1. International Statistical Classification of Diseases and Related Health Problems (10th Revision) (ICD-10) (Version 2.22 dated December 21, 2022).

2. Order of the Ministry of Health of the Russian Federation No. 804n dated October 13, 2017, "On Approval of the Nomenclature of Medical Services."

3. Federal Law No. 323-FZ dated November 21, 2011 «On the Fundamentals of Protecting the Health of Citizens in the Russian Federation».

4. Order of the Ministry of Health of the Russian Federation No. 633n dated October 24, 2025, "On Approval of the Procedure for Providing Medical Care to Adult Patients with the Profile 'Ophthalmology'."

5. Order of the Ministry of Health of the Russian Federation No. 614n dated October 9, 2025, "On Approval of the Procedure for Providing Medical Care to Pediatric Patients with the Profile 'Ophthalmology'."

Appendix B. Physician Action Algorithms

Diagram 1. Algorithm for managing a patient with postoperative intraocular inflammation (differential diagnosis of acute endophthalmitis and other types of intraocular inflammation)

Diagram 2. Algorithm for surgical treatment of a patient with the clinical diagnosis of "endophthalmitis"

Appendix C. Patient Information

Endophthalmitis is one of the most severe complications in ophthalmic surgery. In this condition, the prognosis for preserving visual functions is doubtful and depends on the timely seeking of medical care, as well as the type and virulence of the microorganisms. Rehabilitation after this complication is quite prolonged, ranging from 6 to 12 months.

Following surgical treatment for endophthalmitis, patients must continue instilling the eye drops prescribed by the ophthalmologist. The duration of treatment depends on the severity of the inflammatory process and the patient's individual characteristics. The duration of treatment is determined by the local ophthalmologist who provides dynamic follow-up of the patient.

Following treatment for endophthalmitis, the patient must be informed about strict restrictions for 1 month regarding visiting public baths, saunas, swimming pools, and swimming in open bodies of water. Additionally, physical exertion and sports activities must be restricted for 1 month.

The patient must strictly follow all medical recommendations. If visual functions of the operated eye decline, the patient must immediately consult an ophthalmologist.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

None.