Link Found Between Postreceptor Functional Loss and AMD Retinal Thinning

Links have been discovered between intermediate age-related macular degeneration (AMD) exhibit ganglion cell complex (GCC) thinning and reduced elliposoid zone (EZ) "normalized" reflectivity.

A retrospective case-control study led by Enrico Borrelli (pictured), MD, with the Doheny Eye Institute at the UCLA, and colleagues assert that despite AMD being classified as an "outer retinal disease" there is evidence suggesting that "inner layers are also affected from an early stage of the disease."

The study summarizes several hypotheses about retinal thinning and AMD, but focuses on the "postreceptor functional loss hypothesis," which theorizes that photoreceptor death in AMD may initiate "a cascade of neuronal death and retinal remodeling." Borrelli and colleagues state that their study results support the idea that postreceptor retinal neuronal loss contributes to thinning in patients with intermediate AMD.

Borrelli and colleagues investigated the postreceptor functional loss hypothesis using spectral-domain optical coherence tomography (SDOCT) to evaluate the thickness of the GCC and photoreceptor alterations in AMD, including alterations to the EZ. The study included 68 participants, aged 50 or over, diagnosed with intermediate AMD via optical coherence tomography (OCT) imaging, and ophthalmologic examination. The control group, of 50 similar-aged subjects, were without optic nerve and retinal disease as determined by OCT and ophthalmologic examination.

During the study GCC and drusen thickness were recorded via OCT, and a series of 7 OCT images, in conjunction with a "normalizing" algorithm, were used to determine normalized brightness values for EZ reflectivity. Study data determined that patients in the AMD group (69.34 µm ± 9.30, p<.0001) had slightly thinner GCC thicknesses in comparison to the control group (78.57 µm ± 6.28, p<.0001).

Of the 68 AMD patients, 43 eyes showed normal/average GCC thickness, and 25 showed borderline/reduced average GCC thickness. All control eyes showed normal GCC thickness. Data also showed that EZ "normalized reflectivity" was only slightly decreased in the AMD group (0.61 ± 0.09, p= .006) versus the control group (0.67 ± 0.11, p=006), but was significantly decreased in the 25 eyes designated borderline/reduced average GCC thickness (0.55 ± 0.09). Area and volume of drusen in AMD group did not differ between the 43 eyes with normal GCC thickness, or the 25 eyes with borderline/reduced GCC thickness.

Study data suggests a significant relationship between GCC thickness and "normalized" EZ reflectivity in AMD patients, while "no relationship between these two parameters was seen in healthy eyes." Borrelli and colleagues purport that the results show "some pathologic dependence" between GCC thickness and EZ reflectivity "at least on OCT," and have "confirmed that the inner retinal layers are affected in intermediate AMD."

Borrelli told MD Magazine that relationships between AMD, GCC thickness, and EZ "normalized" reflectivity could play a factor in increasing early identification of AMD, preventing further damage.

"Damage of the GCC thickness in intermediate AMD eyes, which are characterized by large drusen and/or pigmentary abnormalities, might represent a more advanced stage of the disease, in which a pathological dysregulation between photoreceptors and retinal ganglion cells has already occurred,” Borrelli said. “The early identification of this dysregulation, perhaps by identifying those eyes characterized by reduced EZ ‘normalized’ reflectivity and normal GCC thickness, might play a role in preventing further AMD alterations.”

Borrelli noted that study data may assist clinicians and surgeons with AMD treatment and diagnoses. He added that most clinicians and surgeons focus on “preventing the integrity and function” of the unit comprised of photoreceptors, retinal pigment epithelium, Bruch’s membrane, and choriocapillaris, but that “the retinal ganglion cell damage should be thus investigated in these eyes, since it might explain, at least in part, AMD patients’ visual disturbances."

The article "Postreceptor neuronal loss in intermediate age-related macular degeneration" appears online in American Journal of Ophthalmology.

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