Bloodshot Eyes: Cracking the Code of Retinal Vascular Disorders

Retinal vascular diseases, including diabetic retinopathy, are among the most common causes of visual loss globally, both in developed and developing countries. To help address the issue, experts discussed the latest concepts and trends for the diagnosis and management of these eye conditions at the 15th Asia-Pacific Vitreo-retina Society (APVRS 2022) Congress held in Taipei, Taiwan, on November 18 to 20.

Retinal microvascular abnormalities masquerading as neovascular AMD

Traditionally, the onset of ‘exudation’ or ‘neovascularization’ in age-related macular degeneration (AMD) was defined by the identification of retinal fluid and/or hemorrhage. However, advances in imaging have improved our ability to detect ‘non-exudative’ macular neovascularization (MNV), according to Dr. K. Bailey Freund from the US.

He noted that in eyes with non-neovascular AMD, subretinal fluid may occur with acquired vitelliform lesions (AVLs), soft drusen, and drusenoid pigment epithelial detachments (PEDs). Meanwhile, intraretinal exudation causing edema can originate from native retinal vessels within the deep vascular complex (DVC).

Dr. Freund also mentioned that retinal microvascular abnormalities that seem to be influenced by specific AMD features, including intraretinal hyperreflective foci, may masquerade as type 3 MNV.

“Through our collaboration with Dr. Christine Curcio, we found that hyperreflective foci are often fully pigmented, nucleated cells which originate from the retinal pigment epithelium (RPE) layer. These cells can be found contacting vessels of deep capillary plexus, where they may play a role in inducing vascular leakage,” he said, adding that mild intraretinal exudation due to these lesions can vary during follow-up without progression to MNV.

Vascular factors in pathologic myopia

Posterior staphyloma is the hallmark of pathologic myopia. Its risk increases significantly after the age of 50 and in eyes with a longer axial length, noted Yun Hsia from Chinese Taipei.

“The excessive stretching of the ocular coats causes scleral thinning, choroidal attenuation, and loss of outer retina, and is associated with an increased risk of having myopic atrophic maculopathy (MAM), myopic neovascular maculopathy (MNM), and myopic traction maculopathy (MTM),” she said. 

Nevertheless, thinning of the choroid and decreased choroidal perfusion could occur early in the development of myopia. She noted that in MAM, those with tessellated fundus had thinner subfoveal choroid than those with normal appearance of fundus. Eyes with more severe MAM also had thinner choroids. “The severity of MAM was better correlated with thinning of the choroid than that of sclera,” Hsia added.

Also, eyes with impaired choroidal perfusion are prone to MAM. “The presence of peripapillary diffuse choroidal atrophy in highly myopic children is an indicator of the development of advanced myopic maculopathy later. Choroidal thickness is an independent predictor for MAM progression, adjusted for age, gender, axial length, and baseline severity of maculopathy,” she continued.

“Therefore, progressive loss of choroid and impairment of blood flow may have a role in the pathogenesis of myopic maculopathy, especially in MAM and MNM, and correlates with disease severity. The choroid may play an active role in the development of myopia and maculopathy rather than just being a passive response to the stretching of the ocular coat. Longitudinal studies are needed to verify the causal relationship between choroidal perfusion and pathological myopia,” Hsia concluded.

Predicting DR severity

Currently used optical coherence tomography angiography (OCTA) parameters to quantify retinal vasculature in diabetic retinopathy (DR) are non-perfusion area (NPA) and vessel density (VD). However, Prof. Eungsuk Kim from the Kyung Hee University Hospital in South Korea found through his previous study that NPA was a more sensitive parameter than VD for determining the three stages in non-proliferative diabetic retinopathy (NPDR).

In a more recent study, Prof. Kim used the swept-source optical coherence tomography angiography (SS-OCTA) to analyze retinal slabs of 3×3 mm and 12×12 mm, and identify capillary NPA of 170 patients with diabetes mellitus (DM). He found that the combined use of NPA from SS-OCTA and macular ganglion cell-inner plexiform layer thickness (mGCIPL) thickness from optical coherence tomography (OCT) can generate a more accurate predictive value for DR grading.

In terms of non-perfusion in DR, Prof. Kim noted that diabetic microangiopathy starts in the mid-periphery and extends towards the posterior pole with progressive disease severity.

“Multiple and overlapping feeding arterioles compensate for retinal perfusion within the macula. In our study, mGCIPL thickness was significantly correlated with NPA in the 12×12 mm scan, but not in the 3×3 mm scan. This suggests that mid-peripheral capillary non-perfusion occurs in conjunction with macular neuro-degeneration in early DR. Once DR has progressed, microangiopathy extends to the macular area following mGCIPL thinning,” he explained.

“Further studies should elucidate the topographic steps of NPA development and possible association with glaucoma progression in DR,” Prof. Kim suggested.

Detecting microaneurysms in DR

Diabetic macular edema (DME) is a major cause of vision loss in patients with DR. In treating DME, it is important to have an accurate detection of the retinal capillary aneurysm (MA) because direct laser coagulation of MAs is effective when the MA is the cause of DME, according to Dr. Hiroto Terasaki from Kagoshima University, Japan.

He and his colleagues conducted a retrospective observational study to compare the sensitivity and positive predictive value of MA detection by color multicolor scanning laser ophthalmoscopy (SLO), OCTA, and color fundus photography. Color provides information and is sometimes critical in decision-making, he noted.

“Results show that sensitive and positive predictive value is the highest in color SLO (MC), followed by OCTA and fundus photography,” he said.

To investigate the effect of fluorescence leakage on MA detection, the researchers also classified MAs into three groups by comparing the area of fluorescence leakage from MAs at 30 seconds, 90 seconds, and 5 minutes. They found that MAs with early leakage tend to be more detectable than MAs with weak leakage in color SLO, while MAs with early leakage tend to be less detectable in OCTA.

“In conclusion, color SLO is useful for non-invasive MA detection,” he said. 

Editor’s Note: The 15th Congress of the Asia-Pacific Vitreo-retina Society (APVRS 2022) was held on November 18 to 20, 2022, in Taipei, Taiwan. Reporting for this story took place during the event. A version of this article was first published in PIE Magazine Issue 24X – Posterior Segment Special Report.

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