Retinal Perfusion and Injury in Sepsis and after Major Surgery

Abstract

Objective: Assess retinal perfusion in sepsis, compared with uncomplicated postoperative care and healthy controls, and assess the effects of reduced perfusion on retinal structure and visual function.

Design: We conducted a prospective observational cohort study between March 2018 and December 2022, with follow-up measures collected 3 to 6 months after discharge.

Subjects: Twenty-four patients with sepsis were assessed in the intensive care unit (ICU) and 3 to 6 months later, 45 ICU control patients assessed during elective ICU admission after upper gastrointestinal cancer surgery, preoperatively, and 3 to 6 months later, and 15 healthy controls.

Testing: Assessments included retinal layer thickness using OCT, retinal perfusion using OCT angiography, and visual function using Humphrey visual field analysis. Organ dysfunction was assessed by Sequential Organ Failure Assessment (SOFA) scoring.

Main outcome measures: Superficial vascular plexus (SVP) retinal perfusion, OCT retinal ganglion cell layer (GCL) thickness, and mean deviation (MD) on Humphrey visual field testing were evaluated.

Results: Superficial vascular plexus retinal perfusion was 37.4% lower in patients with sepsis compared with ICU control patients (P < 0.001) and 59.7% lower than in healthy controls, which returned to normal by final follow-up. Retinal perfusion correlated with the SOFA score (Pearson r = -0.57, P < 0.001) and weakly correlated with C-reactive protein (r = -0.337, P = 0.01) and mean arterial pressure (r = 0.354, P = 0.006). In patients with sepsis and ICU controls, retinal perfusion in the ICU predicted subsequent GCL thickening, with every 1-unit decrease in SVP sum predicting a 1.88 μm increase in GCL thickness at follow-up (P = 0.003), and worsening visual field MD, with every 1-unit decrease in SVP sum predicting a 0.078 decibel lower MD (P = 0.023).

Conclusions: Retinal perfusion was impaired in patients with sepsis compared with both healthy controls and patients after major surgery. It was moderately associated with other measures of organ dysfunction assessed by SOFA. Reduced retinal perfusion in both patients with sepsis and patients after major surgery is strongly associated with subsequent GCL thickening and less strongly associated with decreased visual field MD, suggesting reduced retinal perfusion is associated with retinal damage, with consequent visual dysfunction.

Financial disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: GCL; OCT; OCTA; Retinal perfusion; Sepsis.

Figure 1

Study flowchart. ICU = intensive care unit; OD = right eye; OS = left eye; post-op = postoperative; pre-op = preoperative.

Figure 2

A–B, Box and whisker plots of macula SVP retinal perfusion at each timepoint for healthy controls, ICU controls, and patients with sepsis assessed by sum (A) and FAZ area (B). Healthy controls are shown in gray, ICU control patients are shown in blue, and patients with sepsis are shown in red. C–H, Representative OCTA images of the right eye SVP (C–E) and ICP (F–H) from an ICU control patient preoperatively (C and F), postoperatively (D and G), and at final follow-up (E and H). I–N, Representative OCTA images of the right eye SVP (I–K) and ICP (L–N) from a patient who developed sepsis after upper gastrointestinal cancer surgery, shown preoperatively (I and L), postoperatively with sepsis (J and M), and at final follow-up (K and N). ∗ = P < 0.05, ∗∗ = P < 0.001. Scale bar = 200 μm. At pre-op: ICU controls n = 44, healthy controls n = 15; at post-op/sepsis: ICU controls n = 34, sepsis n = 24; at follow-up: ICU controls n = 28, sepsis n = 7. FAZ = foveal avascular zone; follow-up = 3 to 6 month follow-up; ICP = intermediate capillary plexus; ICU = intensive care unit; OCTA = OCT angiography; pre-op = preoperative; post-op/sepsis = postoperative for intensive care unit control patients and inpatient care in intensive care unit for patients with sepsis; SVP = superficial vascular plexus.

Figure 3

Scatter plots showing associations between macula SVP retinal perfusion and systemic clinical and laboratory measures, including vasopressor dose. Intensive care unit control patients are shown in blue; patients with sepsis are shown in red. (A–K) Sum retinal perfusion. (L–V) FAZ area. All Pearson r correlation values and corresponding P values are displayed for each plot. CRP = C-reactive protein; FAZ = foveal avascular zone; Hb = hemoglobin; ICU = intensive care unit; MAP = mean arterial pressure; PO2/FiO2 = ratio of partial pressure of oxygen to fraction of inspired oxygen; SOFA = Sequential Organ Failure Assessment; SVP = superficial vascular plexus.

Figure 4

Changes in GCL thickness and Humphrey visual field MD. (A) Box and whisker plot of ETDRS grid area GCL thickness (μm) at each timepoint. (B) Box and whisker plot of MD (dB) at preoperative and follow-up timepoints only. Intensive care unit control patients are shown in blue; patients with sepsis are shown in red. (C–D) Scatter plots of the association between SVP sum retinal perfusion in ICU assessments and subsequent change in GCL thickness at follow-up in each central ETDRS grid area (central, C0; inferior, I1; nasal, N1; superior, S1; temporal, T1) in patients with sepsis (C) and ICU control patients (D). At pre-op: ICU controls n = 44; at post-op/sepsis: ICU controls n = 34, sepsis n = 24; at follow-up: ICU controls n = 28, sepsis n = 7. (E) Scatter plot of the association between SVP sum retinal perfusion in ICU and MD at follow-up in both patients with sepsis and ICU control patients. At pre-op: n = 23; at follow-up: ICU control n = 21, sepsis n = 4. dB = decibels; GCL = ganglion cell layer; ICU = intensive care unit; MD = mean deviation; post-op/sepsis = postoperative for intensive care unit control patients and inpatient care in intensive care unit for patients with sepsis; pre-op = preoperative; SVP = superficial vascular plexus.