Areas of uncertainty in endophthalmitis care

Table 1 Domains of diagnostic uncertainty in endophthalmitis

Domain	Key sources of uncertainty	Clinical implications
Clinical	(1) Overlap in presenting features between infective and non-infective intraocular inflammation; (2) Variable severity at presentation (early, indolent, or partially treated infections); (3) Atypical presentations in immunocompromised or elderly patients; and (4) Rapid inflammatory responses in toxic or immune-mediated conditions mimicking infection	(1) Clinical severity alone cannot reliably distinguish infection from sterile inflammation; (2) Risk of delayed treatment in true infection or overtreatment in non-infective cases; and (3) Necessitates probabilistic decision-making rather than binary diagnosis
Microbiological	(1) High rates of culture negativity despite clinically presumed infection; (2) Prior antibiotic exposure reducing yield; (3) Fastidious or low-virulence organisms; (4) PCR positivity without viable organisms; and (5) Unclear significance of low microbial DNA copy numbers	(1) Absence of culture growth does not exclude infection; (2) PCR results require cautious interpretation and clinical correlation; and (3) Microbiological data often lag behind therapeutic decision-making
Imaging	(1) B-scan ultrasonography lacks specificity for infective vs sterile vitritis; (2) OCT findings reflect secondary inflammatory damage rather than etiology; (3) Widefield imaging documents extent but not cause of inflammation; and (4) Limited ability to predict microbial virulence or disease trajectory	(1) Imaging serves as an adjunct rather than a diagnostic arbiter; (2) Risk of over-interpreting nonspecific structural changes; and (3) Imaging cannot replace clinical and microbiological synthesis
Systemic/etiologic context	(1) Absence of identifiable ocular breach does not exclude infection; (2) Presence of a breach does not exclude toxic or immune-mediated reactions; (3) Subclinical or occult systemic infections; and (4) Masquerade syndromes (e.g., vitreoretinal lymphoma)	(1) Difficulty distinguishing endogenous infection from non-infective masquerade syndromes; (2) Requires parallel systemic evaluation and longitudinal reassessment; and (3) Misclassification may lead to inappropriate therapy or delayed diagnosis

PCR: Polymerase chain reaction; OCT: Optical coherence tomography.

Table 2 Key differences between Endophthalmitis Vitrectomy Study and Complete Early Vitrectomy for Endophthalmitis

Domain	EVS	CEVE
Ref.	Chen et al[10], 2021	Dib et al[3], 2020
Study design	Prospective, randomized multicenter trial	Retrospective cohort/treatment paradigm
Era and technology	20-gauge vitrectomy, limited visualization	Small-gauge, wide-angle, high-cut-rate vitrectomy
Primary trigger for vitrectomy	Presenting visual acuity (LP vs HM or better)	Fundus visibility and disease severity
Timing of surgery	Immediate vitrectomy is mainly for LP eyes	Early vitrectomy when the posterior view is obscured
Extent of vitrectomy	Core vitrectomy; no routine PVD induction	Maximal safe vitrectomy; cortical purulence removal
Treatment philosophy	Conservative, protocol-driven thresholds	Proactive, low threshold for surgery and retreatment
Outcome interpretation	The benefit is limited to the LP subgroup	Favourable outcomes reported across the wider VA spectrum
Generalizability today	Foundational but era-specific	Reflects contemporary surgical capability

EVS: Endophthalmitis Vitrectomy Study; CEVE: Complete Early Vitrectomy for Endophthalmitis; LP: Light perception; HM: Hand movements; PVD: Posterior vitreous detachment; VA: Visual acuity.

Table 3 Geographic variability in endophthalmitis: Microbiology, resistance patterns, and clinical implications

Region/setting	Ref.	Dominant microbial pattern	Key resistance/risk signal	Practical clinical implication
North America/Western Europe	Flynn et al[52], 2008	Coagulase-negative Staphylococcus, Staphylococcus aureus	Rising fluoroquinolone resistance; preserved susceptibility to intravitreal first-line agents	Standard empirical regimens generally effective, but ongoing surveillance required
South Asia	Topol et al[112], 2019	Higher burden of Gram-negative organisms (Pseudomonas, Klebsiella) and fungi	Increasing resistance to fluoroquinolones and cephalosporins	Broader empirical coverage; early consideration of fungal infection
East Asia	Wong et al[113], 2000	Mixed Gram-positive/Gram-negative spectrum; higher streptococcal prevalence	Marked regional variability; limited standardized resistance data	Local microbiological data essential for empirical decision-making
Middle East	Shams Abadi et al[114], 2023; Falavarjani et al[115], 2012	Predominantly Gram-positive; Gram-negative organisms in trauma	Emerging multidrug-resistant Gram-negative isolates	Trauma-associated cases may warrant early surgery and tailored therapy
Africa	Solomon et al[116], 2025	Higher proportion of post-traumatic and endogenous infections	Sparse resistance data; limited laboratory infrastructure	Empirical management common; need for regional registries and surveillance
Latin America	Morris et al[53], 2021	Heterogeneous spectrum (Gram-positive, Gram-negative, fungal)	Increasing resistance reported in tertiary centers	Empirical therapy often requires regional customization
Post-traumatic Endophthalmitis (Global)	Mitra et al[117], 2021; Long et al[118], 2014	Bacillus spp., Gram-negative organisms	High virulence predominates over resistance	Early vitrectomy and aggressive therapy prioritized
Endogenous Endophthalmitis (Global)	Kuhn et al[54], 2006	Candida, Aspergillus, Gram-negative bacteraemia-associated organisms	Resistance influenced by prior systemic antimicrobial exposure	Requires systemic source control and prolonged, coordinated therapy

Bacillus spp.: Bacillus species.