# Endogenous endophthalmitis complicating infective endocarditis: a multicentre case-matched control cohort

Iris Layani, Florent Arregle, Sebastian Santos Patarroyo, Aurore Aziz, Julien Mancini, Julien Ternacle, Peter Laursen Graversen, Emil Foesbol, Nuria Fernández-Hidalgo, Marco Tomasino, et al.

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## To cite this version:

Iris Layani, Florent Arregle, Sebastian Santos Patarroyo, Aurore Aziz, Julien Mancini, et al., Endogenous endophthalmitis complicating infective endocarditis: a multicentre case-matched control cohort. European Heart Journal Open, 2025, 5 (6), pp.oeaf136. 10.1093/ehjopen/oeaf136. hal-05369372

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# Endogenous endophthalmitis complicating infective endocarditis: a multicentre case-matched control cohort

Iris Layani<fnref n="1" />,†, Florent Arregle<fnref n="1" />,†, Sebastian Santos Patarroyo², Aurore Aziz³, Julien Mancini⁴, Julien Ternacle⁵,⁶, Peter Laursen Graversen ID ⁷, Emil Foesbol⁷, Nuria Fernández-Hidalgo ID ⁸, Marco Tomasino ID ⁹, Antonia Sambola ID ⁹, Audrey Le Bot¹⁰, Pierre Tattevin ID ¹⁰, Christophe Tribouilloy ID ¹¹, Claire Lucas<fnref n="1" />, Elisabeth Botelho-Nevers ID ¹²,¹³, David Boutoille ID ¹⁴, Mary Philip ID <fnref n="1" />, Sandrine Hubert<fnref n="1" />, Neil Tadrist³, Natacha Stolowy³, Nahema Issa ID ¹⁵, Frédérique Gouriet¹⁶, Larry M. Baddour ID ²,‡, and Gilbert Habib ID <fnref n="1" />,*‡

Received 13 July 2025; revised 26 August 2025; accepted 12 September 2025; online publish-ahead-of-print 17 October 2025

Handling Editor: Patrizio Lancellotti

## Aims

Endogenous endophthalmitis (EE) is a rarely reported complication of infective endocarditis (IE). In an international series, we sought to determine the clinical and microbiological profile, treatment, and outcome of patients presenting with IE-related EE.

## Methods and results

Cases recorded from 2014 to 2023 in nine centres in Europe and the United States were collected. Results were compared to a matched control group.

## Conclusion

Sixty-six patients with EE were reported, mean age of 65.2 ± 14.9 years, 71% (n = 47) male. Blood cultures were positive in 97% (64 cases) of patients, with a predominance of streptococci (46%, n = 30).

As compared with the control group (n = 264), the EE group presented with more frequent diabetes (35% vs. 21%, P = 0.02), history of cirrhosis (9% vs. 3%, P = 0.04), glomerulonephritis (15% vs. 0.4%, P < 0.001), embolism before admission (92% vs. 55%, P < 0.001), and Janeway lesions (9% vs. 1%, P = 0.002). Streptococcal infection (46% vs. 26%, P = 0.001) was more frequent and Enterococcal infection (0% vs. 18%, P < 0.001) less frequent in the EE group.

<footnote n="1">¹Department of Cardiology, La Timone Hospital Marseille, Boulevard Jean Moulin 13005, Marseille, France; ²Division of Public Health, Infectious Diseases and Occupation Medicine, Department of Medicine, Mayo Clinic, 200 First Street SW | Rochester, MN 55905, United States; ³Department of Ophthalmology, Hospital Nord and Conception, Aix-Marseille University, Bd Jean Moulin 13005 Marseille, France; ⁴Aix-Marseille University, APHM, INSERM, IRD, SESSTIM, Hop Timone, Public Health Department, BIOSTIC, Boulevard Jean Moulin 13005 Marseille, France; ⁵Unité Médico-Chirurgique des Valvulopathies Hôpital Cardiologique Haut-Lévêque, CHU de Bordeaux, Avenue Magellan, Pessac 33600, France; ⁶Centre de Recherche Cardio-Thoracique de Bordeaux, Univ. Bordeaux, INSERM, U1045, Avenue Magellan, Pessac F-33604, France; ⁷Department of Cardiology, Copenhagen University Hospital—Rigshospitalet, Blegdamsvej 9 2100, Copenhagen, Denmark; ⁸Servei de Malalties Infeccioses, Hospital Universitari Vall D'Hebron, Paseo de la Vall d'Hebron, 119-129 Barcelona, Spain; ⁹Department of Cardiology, University Hospital Vall D'Hebron, Paseo de la Vall d'Hebron 119-129, Barcelona, Spain; ¹⁰Infectious Diseases and Intensive Care Unit, Pontchaillou University Hospital, rue Abbé Huet 2 r Henri Le Guilloux, Rennes, France; ¹¹Department of Cardiology, Amiens University Hospital, 1 rond-point du Professeur Christian Cabrol 80054, Amiens, France; ¹²Infectious Diseases Department, University Hospital of Saint-Etienne, 25 bd Pasteur, Saint-Etienne cedex 2 42055, Saint Etienne, France; ¹³13CIRI—Centre International de Recherche en Infectiologie, Team GIMAP, Université Jean Monnet, 10, Rue Tréfilerie - CS 8230142023 Saint-Etienne Cedex 2, Université de Lyon, Inserm, U1111, CNRS, UMR530, Saint-Etienne F42023, France; ¹⁴Maladies Infectieuses et Tropicales—CHU de Nantes 1 place Alexis-Ricordeau 44093, Nantes, Cedex; ¹⁵Service de Médecine Interne et Maladies Infectieuses, Hôpital Saint-André, CHU de Bordeaux, 1 r Jean Burguet, 33000 Bordeaux, France; and ¹⁶Institut Hospitalo-Universitaire Méditerranée Infection, Boulevard Jean Moulin, 13005 Marseille, France</footnote>

<footnote>* Corresponding author. Tel: +33491387588 Email: gilbert.habib3@gmail.com</footnote>

<footnote>† Iris Layani and Florent Arregle equally contributed to this work and are co-first authors.</footnote>

<footnote>‡ Larry M. Baddour and Gilbert Habib are co-last authors.</footnote>

<footnote>© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.</footnote>
The main ocular symptoms were a decrease in visual acuity (96%), red eye (55%), and ocular pain (55%). Treatment of EE consisted of intravitreal antibiotic injection in 55 (83%) patients and vitrectomy in 17 (26%). Improvement of visual acuity was observed in 36 (55%) patients.

## Conclusion

EE is a serious complication of IE with severe residual vision impairment. Patients with IE should be evaluated for ocular complications, since early detection of EE is crucial to prevent delays in management and to preserve visual function.

## Graphical abstract

* ✓ Endogenous endophthalmitis (EE) is a rare but serious complication of infective endocarditis (IE) with severe residual vision impairment.

* ✓ In a multicenter series, 66 patients with EE were compared to a control group of 264 IE without EE

* ✓ Patients with EE complicating IE presented with more frequent diabetes, history of cirrhosis, glomerulonephritis, embolism and streptococcal infection, and less frequent enterococcal infection than the control group

* ✓ Patients with IE should be evaluated for ocular complications, since early detection of EE is crucial to prevent delays in management and to preserve visual function.

<figure><img src="image_3.png" /><figcaption>Frontal intraoperative photograph of the right eye showing a severe endogenous endophthalmitis complicating infective endocarditis in an intravenous drug addiction patient</figcaption></figure>

## Keywords

Infective endocarditis • Ocular complications • Cohort • Endophthalmitis

Endogenous endophthalmitis (EE) results from bacterial or fungal infection involving the vitreous and/or aqueous humours.¹ Although a rare condition, it is frequently complicated by blindness and loss of the affected eye.² Up to 15% of endophthalmitis cases are endogenous, due to haematogenous spread of organisms from extraocular sites, with infective endocarditis (IE) being the most common source.¹,³ EE resulting from IE has been documented primarily in case reports.⁴ A recent retrospective study focused on predictive factors of EE complicating IE,⁵ but did not include data on microbiology or patient outcomes. In this international investigation, we aimed to determine the clinical features, treatment, and outcomes of patients presenting with EE complicating IE.

## Materials and methods

Cases between 2014 and 2023 were included, and data were collected from the local IE registries of nine hospitals across Europe and the USA (see Supplementary material online, Table). Patients were included if they had definite IE according to the Duke⁶ or ESC criteria⁷ and presented with associated EE. Patients were compared to a 4:1 matched control group of IE patients without EE (matching on the nearest date of diagnosis from La Timone, Marseille, IE cohort).

The diagnosis of EE was based on a combination of clinical, microbiological (from blood cultures, intraocular samples from the anterior

chamber or vitreous for Gram staining, culture (bacteria or fungi), and/or PCR), and imaging findings. Visual acuity was expressed in logarithms of the Minimum Angle of Resolution (logMAR) units, in accordance with international ophthalmology standards. On this scale, higher logMAR values indicate poorer visual acuity, while lower values (approaching zero or negative) indicate better vision. For reference, 0.0 logMAR corresponds to 20/20 Snellen equivalent, 0.4 logMAR to approximately 20/50, and 1.0 logMAR to approximately 20/200. Severe impairment was defined as visual acuity worse than 0.4 logMAR (≈20/50) in the affected eye. Patients were classified as legally blind when visual acuity was worse than 1.0 logMAR (≈20/200) at follow-up. The thresholds used in this study are consistent with the U.S. definition of legal blindness (best-corrected visual acuity of 20/200 or worse in the better-seeing eye, or visual field ≤ 20 degrees) as established by the Social Security Administration⁸ and are broadly aligned with the World Health Organization (WHO) classification of vision impairment.⁹ For patients with bilateral EE, visual acuity was assessed separately for each eye. For statistical analysis and classification of visual outcomes (e.g. severe impairment, legal blindness), the value from the eye with the worst visual acuity at follow-up was used. This approach was chosen to reflect the maximum degree of functional impairment experienced by the patient and to avoid underestimating vision loss in bilateral cases.

<footnote>* Septic melting of the corneal stroma</footnote>

<footnote>** Major bulbar and tarsal conjunctival hyperemia</footnote>
Data collected included demographic information, comorbidities, clinical signs and symptoms, echocardiographic findings, microbiological results, and follow-up information, including ophthalmic surgery and outcome of endophthalmitis (visual recovery, complications, and recurrences).

Categorical variables were expressed as percentages (counts) and compared using X² or Fisher's exact tests. Continuous variables were expressed as mean ± standard deviation (SD) and compared using Student t-tests. The visual acuity (logMAR scale) was expressed as median [minimum–maximum]. Analyses were performed using IBM SPSS Statistics 20.0 (IBM Inc., New York, USA).

## Ethical and regulatory aspects

Each centre complied with its national ethical and regulatory standards. All patients included gave consent for this protocol.

## Results

Sixty-six patients with EE complicating IE were included (10 patients from the USA and 56 patients from Europe) and were compared to 264 control patients. Mean age was 65.2 years (± 15), with a male predominance of 71% (n = 47). Among comorbidities, EE patients had more diabetes mellitus (35% vs. 21%, P = 0.02) and cirrhosis (9% vs. 3%, P = 0.04) compared to the control group, but less atrial fibrillation (18% vs. 33%, P = 0.02) (Graphical Abstract).

### Clinical symptoms of IE

In the EE group, 56 (85%) IE were community-acquired, and 4 patients had injection drug use. More patients in the EE group presented with septic shock (18% vs. 8%, P = 0.02). Janeway lesions (9% vs. 1%, P = 0.002), glomerulonephritis (15% vs. 0.4%, P < 0.001), and systemic embolism (92% vs. 55%, P < 0.001) were more frequent in the EE than in the control group (Table 1).

### Echocardiography

Most patients (n = 59, 89%) had left-sided IE, while only 8% had right-sided IE, which was significantly lower than in the control group (18%, P = 0.04). There were no cases of bilateral IE. Most patients had native valve IE (68%). Vegetations were identified in 82% of patients, including aortic valve, mitral valve, and tricuspid valve vegetations in 39% (n = 22), 49% (n = 29), and 9% (n = 5), respectively. Annular complications occurred in 17% of patients.

### Microbiology

Blood cultures were positive in 97% of patients in the EE group compared to 87% of patients without EE (P = 0.02) and showed a predominance of streptococci and *Staphylococcus aureus*. When compared to the control group, EE patients had significantly more streptococci infection (46% vs. 26%, P = 0.001) and less enterococci infection (0% vs. 18%, P < 0.001).

### Ocular symptoms, treatment and outcome

EE affected the right eye more frequently (74%, n = 49) than the left eye (59%, n = 39) and 33% (n = 22) of patients had bilateral involvement. EE diagnosis was suspected in the presence of symptoms including vision loss in 96% (n = 63) of patients, pain (55%, n = 36), and red eye (55%, n = 36) (Table 2 and Graphical Abstract).

Intravitreal antibiotic injections were performed in 83% (n = 55) of patients. Vancomycin was the most frequently used (71%, n = 47) anti-microbial, followed by ceftazidime (49%, n = 32), and amphotericin B in 6% (n = 4) of patients. Vitrectomy was performed in 26% (n = 17) of patients.

<table><caption>**Table 1** Clinical characteristics, microbiology, echocardiographic findings, and outcome of 66 cases of endophthalmitis complicating infective endocarditis compared to a control group</caption><thead><tr><th></th><th>Endophthalmitis<br>n = 66 (%)</th><th>Control<br>n = 264 (%)</th><th>P</th></tr></thead><tbody><tr><td>Male</td><td>47 (71)</td><td>195 (74)</td><td>0.6</td></tr><tr><td>Age<sup>a</sup></td><td>65.2±14.9</td><td>66±14.6</td><td>0.8</td></tr><tr><td>Medical history</td><td></td><td></td><td></td></tr><tr><td>Hypertension</td><td>31 (47)</td><td>115 (44)</td><td>0.6</td></tr><tr><td>Diabetes</td><td>23 (35)</td><td>55 (21)</td><td><strong>0.02</strong></td></tr><tr><td>Smoking</td><td>18 (27)</td><td>95 (36)</td><td>0.16</td></tr><tr><td>Atrial fibrillation</td><td>12 (18)</td><td>88 (33)</td><td><strong>0.02</strong></td></tr><tr><td>Chronic renal failure</td><td>11 (17)</td><td>26 (10)</td><td>0.12</td></tr><tr><td>Heart failure</td><td>7 (11)</td><td>49 (19)</td><td>0.12</td></tr><tr><td>Cirrhosis</td><td>6 (9)</td><td>8 (3)</td><td><strong>0.04</strong></td></tr><tr><td>Intravenous drug use</td><td>4 (6)</td><td>20 (8)</td><td>0.8</td></tr><tr><td>Clinical characteristics</td><td></td><td></td><td></td></tr><tr><td>Heart Failure</td><td>14 (21)</td><td>73 (28)</td><td>0.29</td></tr><tr><td>Septic shock</td><td>12 (18)</td><td>22 (8)</td><td><strong>0.02</strong></td></tr><tr><td>Osler's node</td><td>4 (6)</td><td>5 (2)</td><td>0.08</td></tr><tr><td>Janeway lesion</td><td>6 (9)</td><td>3 (1)</td><td><strong>0.002</strong></td></tr><tr><td>Glomerulonephritis</td><td>10 (15)</td><td>1 (0.4)</td><td><strong>&lt;0.001</strong></td></tr><tr><td>Total embolism</td><td>61 (92)</td><td>144 (55)</td><td><strong>&lt;0.001</strong></td></tr><tr><td>Echocardiography</td><td></td><td></td><td></td></tr><tr><td>Left heart</td><td>59 (89)</td><td>223 (85)</td><td>0.31</td></tr><tr><td>Right heart</td><td>5 (8)</td><td>47 (18)</td><td><strong>0.04</strong></td></tr><tr><td>Prosthetic valve</td><td>17 (26)</td><td>94 (36)</td><td>0.13</td></tr><tr><td>Cardiac device-related<br>infective endocarditis</td><td>5 (8)</td><td>31 (12)</td><td>0.33</td></tr><tr><td>Vegetation</td><td>54 (82)</td><td>201 (76)</td><td>0.33</td></tr><tr><td>Microbiology</td><td></td><td></td><td></td></tr><tr><td>Positive Blood culture</td><td>64 (97)</td><td>229 (87)</td><td><strong>0.02</strong></td></tr><tr><td><i>Staphylococcus aureus</i></td><td>20 (30)</td><td>67 (26)</td><td>0.43</td></tr><tr><td>Streptococci</td><td>30 (46)</td><td>68 (26)</td><td><strong>0.001</strong></td></tr><tr><td>Enterococci</td><td>0</td><td>48 (18)</td><td><strong>&lt;0.001</strong></td></tr><tr><td>Gram negative bacilli</td><td>3 (5)</td><td>18 (7)</td><td>0.78</td></tr><tr><td>Fungi</td><td>2 (3)</td><td>2 (0.8)</td><td>0.18</td></tr></tbody></table>

Bold represents significant differences.

<sup>a</sup>Value expressed as mean ± standard deviation.

Vision improvement was observed in 55% (n = 36) of patients (74%, n = 14 in the *S. aureus* group and 52%, n = 15 in the streptococci group). Retinal detachment was present in 11 patients, accounting for 17% of the total cohort. The percentage of patients maintaining a satisfactory level of visual acuity was 30% (n = 20). Conversely, 65% (n = 43) of patients experienced severe impairment. Among them, 30% (n = 20) were classified as legally blind. In-hospital and one-year mortality rates were 16% (n = 11) and 27% (n = 16), respectively. The IE recurrence rate was 4% (n = 2).

## Discussion

This international study provides an analysis of the clinical, microbiological, and outcome characteristics of patients affected by EE in IE.
<table><caption>**Table 2** Ocular symptoms and outcome</caption><thead><tr><th></th><th>Endophthalmitis<br>n = 66 (%)</th></tr></thead><tbody><tr><td>Ocular symptoms</td><td></td></tr><tr><td>Left eye</td><td>39 (59)</td></tr><tr><td>Right eye</td><td>49 (74)</td></tr><tr><td>Bilateral</td><td>22 (33)</td></tr><tr><td>Decreased visual acuity</td><td>63 (96)</td></tr><tr><td>Ocular pain</td><td>36 (55)</td></tr><tr><td>Red eye</td><td>36 (55)</td></tr><tr><td>Conjunctivitis</td><td>18 (27)</td></tr><tr><td>Hypopion</td><td>20 (30)</td></tr><tr><td>Tyndall</td><td>17 (26)</td></tr><tr><td>Hyalitis</td><td>20 (30)</td></tr><tr><td>Intravitreal haemorrhage</td><td>12 (18)</td></tr><tr><td>Roth's spots</td><td>16 (24)</td></tr><tr><td>Retinal detachment</td><td>11 (17)</td></tr><tr><td>Visual acuity before treatment (logMAR)<sup>a</sup></td><td>1.5 (0.2-&gt;2.3)</td></tr><tr><td>Outcome</td><td></td></tr><tr><td>Vision improvement</td><td>36 (55)</td></tr><tr><td>Visual acuity after treatment (logMAR)<sup>a</sup></td><td>0.7 (0-&gt;2.3)</td></tr><tr><td>Severe vision impairment (worse than 0.4<br>logMar, &approx;20/50)</td><td>43 (65)</td></tr><tr><td>Blindness (worse than 1.0 logMar, &approx;20/200)</td><td>20 (30)</td></tr></tbody></table>

On the logMAR scale, higher values indicate poorer visual acuity, and values closer to zero (or negative) indicate better visual acuity.

Although this complication is rare, it often leads to significant functional impairment.

General characteristics of patients in our cohort, such as age and sex, were consistent with those of a recent cohort of IE patients.¹⁰ Comorbidities associated with EE were diabetes mellitus and cirrhosis, as recently reported.⁵

Interestingly, streptococci were the most common pathogens in our cohort, followed by *S. aureus*. No cases of EE complicating *E. faecalis* IE were detected, however. This is an intriguing observation, as most series of IE cases report that enterococci are among the top three IE pathogens.¹⁰ Enterococci were not only not identified in our current series of EE cases, but were not seen among pathogens in an earlier series of EE cases, where IE was the most common source³ or listed as pathogens in a recently published State-of-the-Art review on ocular infections.¹¹ Thus, it is tempting to speculate that certain virulence determinants in EE causation may not be present in IE cases due to enterococci and deserve further study.

Unfortunately, at one-year follow-up, about two-thirds of patients had experienced severe residual visual acuity impairment. This highlights the poor functional prognosis of this complication that has been characteristic in other investigations¹² and warrants evaluation with a thorough history and physical examination in every patient with IE, despite the limited yield in prevalence.⁵

## Limitations

This is a retrospective observational study with inherent limitations, and the small number of patients impairs the robustness of the results. No multivariate analysis was performed due to the small sample size. Moreover, the control group was obtained from a single centre, which

could not be representative of epidemiological data from the other centres.

## Conclusion

EE is a rare but serious complication of IE that commonly results in vision loss. Our investigation highlights a high burden of comorbidities such as diabetes mellitus and cirrhosis, and the prevalence of streptococci in this population. Although infrequent, EE should be evaluated in each IE patient with specific evaluation as part of both the history and physical examination, since early detection of EE is crucial to prevent delays in management and to preserve visual function.

## Lead author biography

<figure><img src="image_4.png" /><figcaption>Gilbert HABIB</figcaption></figure>

## Present Position and Address

* Chair of the Cardiology Department (heart failure, valvular heart disease) La Timone Marseille France.

* Director of the echocardiographic laboratory la Timone Marseille.

## European Society of Cardiology Activities

* President of the European Association of Cardiovascular Imaging 2014–2016

* Chairman of the ESC guidelines on infective endocarditis 2009 and 2015

* Chairman of the EACVI guidelines for the use of echocardiography in infective endocarditis 2010

* Chairman of the EORP/ESC EUROENDO registry 2017–2019

## Major Publications

More than 300 publications in international peer-reviewed journals.

## Data availability

Data, research materials, and analytical methods supporting this study are available through the corresponding author upon reasonable request.

## Supplementary material

Supplementary material is available at *European Heart Journal Open* online.

**Conflict of interest:** None declared.

## Funding

None.

<footnote>ªMedian [minimum-maximum].</footnote>
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