A Large Area of Capillary Nonperfusion May Need Aggressive Intervention

Diabetic Retinopathy
Diabetic Retinopathy Due To Diabetic Hyperglycemic Lesions On The Arterioles. Image Of The Back Of The Eye. (Photo By BSIP/UIG Via Getty Images)
Poor visual outcomes have been described for patients with a large area of capillary nonperfusion, but wide-field FFA may find large regions earlier.

Once diabetes mellitus and diabetic retinopathy (DR) are diagnosed, routine testing often includes fundus photography, but not necessarily fundus fluorescein angiography (FFA) — potentially leaving evolved capillary nonperfusion undetected. A novel case series shows that large areas of capillary nonperfusion (LACNP) are associated with long-term or uncontrolled diabetes, as well as poor visual outcome, according to data published in BMC Ophthalmology.

The FFA image series with 130° viewing area found LACNP in 3.3% of patients diagnosed with DR between January 2017 and December 2019. The retrospective, interventional study included 43 eyes of 24 participants who were DR treatment-naïve and had good-quality angiograms. Large area was defined as more than 70% of the visible retina, with possible macular involvement, and upon imaging, the sample’s mean area of nonperfusion 79.1±8.1%. All had a degree of neovascularization, and angiography showed 58.1% of eyes displayed macular ischemia.

Participants underwent panretinal laser photocoagulation (PRP) sessions. During a mean follow-up time of 12.4±16.7 months, 5 eyes were also treated with combined macular grid laser for continued macular edema, and 17 with anti vascular endothelial growth factor (anti-VEGF) injections for macular edema, neovascular glaucoma, or before pars plana vitrectomy (PPV). Twenty eyes, 46.5% developed advanced proliferative DR (PDR), of which 11 eyes received PPV with or without phacoemulsification, and 4 had surgery to treat glaucoma. At last visit, best-corrected visual acuity worsened in 55.8% of eyes, and stabilized or improved in 44.2%.

Charts indicated the onset of diabetes symptoms averaged 7.3 years. Participants’ baseline average fasting blood glucose measured 13.6 mmol/L, and HbA1c 8.1%. Nine also had hypertension, 37.5%. All patients agreed to intensive therapy for diabetes and hypertension in a hospital setting in addition to ocular treatment, and investigators speculate this factor slowed DR advancement — in LACNP, standard PRP may not be enough to avert complications.

Previous research has shown capillary non-perfusion region size can serve as a biomarker for DR progression; individuals with moderate or severe nonproliferative DR (NPDR) have exhibited approximately 2.7% less area covered by retinal vessels with flow (perfusion index) than those with mild NPDR, and in cases of PDR a 4.3% lower index. Researchers believe that capillary nonperfusion begins at the equator and then expands to the periphery. Also, since the macula has several capillary plexus layers, LACNP here may signal advanced ischemia. 

The current study’s retrospective design precluded assessing impact on VA of elements such as macular edema or cataract. Another limitation was lack of individuals in control groups. 

Researchers suggest early screening and prompt, aggressive treatment may preserve macular microperfusion, along with central vision. “Of note, 8 in 11 eyes receiving anti-VEGF agents and PPV surgery had the visual function improved or maintained with no evidence of DR worsening at a mean follow-up time of 21.0 months,” according to the investigators. “The other 3 eyes showed slight vision decrease without progressing to neovascular glaucoma.” 


Huang Z, Qiu K, Yi J, et al. Diabetic retinopathy with extensively large area of capillary non-perfusion: characteristics and treatment outcomes. BMC Ophthalmol. Published online July, 4 2022. doi:10.1186/s12886-022-02508-6