AT A GLANCE

  • A small retrospective study found that the temporal region is the area of the retina most susceptible to damage in sickle cell disease (SCD).
  • The study suggests that temporal retinal thinning and reduced vascular density may predict the presence of retinopathy in children with SCD.
  • The study authors suggest that temporal centered OCT angiography should be a part of screening for children with SCD.

Sickle cell disease (SCD) is the most prevalent structural hemoglobinopathy in the world. It is associated with multisystemic vascular occlusive events that can affect the retinal microvasculature.

Sickle cell retinopathy (SCR) is the most severe ocular complication of SCD. It is classified either as nonproliferative (NPSCR), with features including peripheral venous tortuosity, salmon-patch hemorrhages, iridescent spots and black sunbursts, or as proliferative (PSCR). Goldberg proposed a five-stage grading system for PSCR.1 Without early detection and treatment, SCR can lead to irreversible vision loss.2

Macular thinning and lower vascular density have been proposed as preclinical alterations preceding SCR development.3 Because these abnormalities are not detected in routine observations, imaging exams are crucial for SCR screening.

We performed a study to analyze the characteristics of the macula and temporal retina in children with SCD.

MATERIALS AND METHODS

This single-center, retrospective study included children less than 18 years old with SCD. Exclusion criteria were high refractive errors (> 6.00 D), media opacities, and retinopathy other than SCR. Approval was obtained from the relevant institutional research committee.

We collected clinical and laboratory data and performed ophthalmologic evaluation including BCVA, slit-lamp observation, and fundoscopy.

Macular OCT and OCT angiography (OCTA) imaging with the Cirrus HD-OCT 5000 with Angioplex (Carl Zeiss Meditec) was performed. Scan protocols included collecting 6x6–mm images centered at the fovea and 3x3–mm images through the temporal macula. Macular thickness, foveal avascular zone (FAZ), and superficial vessel density (SVD) were automatically generated.

Deep vascular density (DVD) was calculated with ImageJ using the method described by Parodi et al.4 Vascular density (VD) was expressed as the ratio between vessel pixels and total area (Figure).

<p>Figure. A deep vascular density (DVD) image generated by ImageJ. On the left is the fovea-centered image; on the right, the temporal retina. At bottom, the output calculated by ImageJ (here, for deep foveal capillary density).</p>

Click to view larger

Figure. A deep vascular density (DVD) image generated by ImageJ. On the left is the fovea-centered image; on the right, the temporal retina. At bottom, the output calculated by ImageJ (here, for deep foveal capillary density).

Statistical analysis was performed using SPSS Statistics 23.0 (IBM). Mann-Whitney tests were used to compare eyes with and without SCR. Statistical significance was defined as P < .05.

RESULTS

Our study included 15 children with SCD; eight had SCR and seven had no SCR. For two children, information could be retrieved from only one eye due to lack of cooperation. Hence, data for 28 eyes were included in the study.

Patients’ mean age was 12 ±4 years. Demographic and laboratory data are presented in Tables 1 and 2, respectively. BCVA was 6/7.5 bilaterally in both the SCR and the no-SCR groups.

Fourteen of 28 eyes (50%) were classified as having NPSCR, and none had PSCR.

OCT data are shown in Table 3. There were no differences regarding foveal thickness between the SCR and no-SCR groups.

The temporal retina tended to be thinner than the fovea, with a thickness of 196.5 ±18.1 µm at 6 mm temporal to the macula. Mean temporal thickness was lower in eyes with retinopathy (185.3 ±16.2 µm vs 205.2 ±13.2 µm, respectively, P < .01). This difference was more pronounced in the temporal subfield of the displaced scan in the temporal retina (184.3 ±16.3 µm vs 196.4 ±10.7 µm, P = .04).

OCTA results are presented in Table 4. Mean FAZ appeared to be larger in the SCR group (0.36 ±0.11 vs 0.30 ±0.1 mm2, P = .46).

Mean foveal VD values were lower in the SCR group than in the no-SCR group, both SVD (37.1 ±1.4% vs 43.3 ±1.7%, P = .01) and DVD (39.1 ±1.2% vs 44.3 ±2.2%, respectively, P = .01). In SCR eyes, the temporal SVD (27.6 ±3.7% vs 37.1 ±2.3, P<0.01) and DVD (32.3 ±2.6% vs 38.3 ±2.1%, P < .01) mean values were also lower.

DISCUSSION

SCR can lead to serious visual impairment if not recognized and treated early. Recent work has led to the detection of certain retinal alterations that can predict the development of proliferative disease, improving early diagnosis and treatment.5-7

In this study in children with SCD, mean foveal SVD and DVD values were lower in eyes with SCR than in eyes with no SCR. However, no difference was seen between the groups regarding foveal thickness. Mean temporal retinal thickness and VD in both plexuses were also lower in eyes with SCR, adding information to previous reports.8

This finding suggests that the temporal macula may be more susceptible to damage due to the small caliber of terminal arterioles. The authors believe that reduced VD could be reliable markers of early retinal damage.

Because these alterations are commonly asymptomatic and most often undetectable in routine ophthalmologic examination, OCTA could be helpful in screening for SCR. It is important to highlight that screening should start early, but there is also a need to establish parameters for OCTA data in healthy children to further help in identifying those at risk for SCR. We propose that temporal retina scans should be part of regular evaluation of children with SCD.

Our results are encouraging and, despite the small sample size, may provide a basis for prospective clinical trials to define the role of OCTA in SCR screening.

1. Goldberg MF. Classification and pathogenesis of proliferative sickle retinopathy. Am J Ophthalmol. 1971;71(3):649-665.

2. Goldberg MF. Natural history of untreated proliferative sickle retinopathy. Arch Ophthalmol. 1971;85(4):428-437.

3. Minnal VR, Tsui I, Rosenberg JB. Central macular splaying and outer retinal thinning in asymptomatic sickle cell patients by spectral-domain optical coherence tomography. Am J Ophthalmol. 2011;152:1074.

4. Parodi MB, Cicinelli MV, Rabiolo A, et al. Vessel density analysis in patients with retinitis pigmentosa by means of optical coherence tomography angiography. Br J Ophthalmol. 2017;101(4):428-432.

5. Lee CM, Charles HC, Smith RT, Peachey NS, Cunha-Vaz JG, Goldberg MF. Quantification of macular ischaemia in sickle cell retinopathy. Br J Ophthalmol. 1987;71(7):540-545.

6. Sanders RJ, Brown GC, Rosenstein RB, Magargal L. Foveal avascular zone diameter and sickle cell disease. Arch Ophthalmol. 1991;109(6):812-815.

7. Hood MP, Diaz RI, Sigler EJ, Calzada JI. Temporal macular atrophy as a predictor of neovascularization in sickle cell retinopathy. Ophthalmic Surg Lasers Imaging Retina. 2016;47(1):27-34.

8. Han IC, Tadarati M, Pacheco KD, Scott AW. Evaluation of macular vascular abnormalities identified by optical coherence tomography angiography in sickle cell disease. Am J Ophthalmol. 2017;177:90-99.