Back of eye research may open new pathways to photoreceptor therapy

Preserving photoreceptor cells important in managing macular pathologies.

Better understanding of the retinal layers, due in part to improvements in imaging capabilities, is leading researchers toward a new paradigm in retinal practice: interventions that can repair, replace or preserve photoreceptor cells.

As light sources and imaging modalities have improved, these devices are capable of producing intricate pictures of retinal histology. This detailed imaging capacity allows researchers to identify pertinent areas of the retina.

One such finding is the realization of the importance of the inner/outer segment (IS/OS) junction in visual function. Several studies using optical coherence tomography have linked a healthy IS/OS junction — the area between the external limiting membrane and the retinal pigment epithelium — with visual recovery after intervention for several macular pathologies.

These studies are a necessary first step for researchers to investigate the functional consequences of structural disruptions, as well as the creation of management strategies to affect photoreceptor viability.

Detailed images of the retina

Advances in OCT technology have produced faster image-taking capability and more precise depictions of retinal architecture. For example, time-domain OCT has provided the platform on which ophthalmic researchers were able to study the impact of structural disturbances on functionality of the eye.

Much research in the past decade has focused on the role of photoreceptor impairment in poor vision secondary to macular pathology. Several studies have already shown that disruptions of the IS/OS junction — most likely indicative of poorly functioning photoreceptor cells — can lead to poor visual prognosis in macular hole and macular edema.

More recently, two studies looked at whether disruptions in the IS/OS junction could explain why some patients did not recover vision after surgery for removal of an epiretinal membrane (ERM).

According to Yoshinori Mitamura, MD, PhD, and colleagues, there is a direct correlation between disruption in the preoperative status of the IS/OS junction and vision after ERM removal, and this finding may imply changes to patient management strategies.

“Our study indicates poor visual outcome in ERM patients with no preoperative IS/OS junction,” Dr. Mitamura said in an interview with Ocular Surgery News. “In my opinion, vitrectomy should be considered as soon as possible if the IS/OS continuity is damaged in the follow-up of ERM patients.”

In the study, the researchers reported a correlation between IS/OS junction status and best corrected visual acuity: The presence of an IS/OS line on OCT correlated with BCVA preoperatively, as well as at 3 and 6 months after surgery.

“Normal preoperative IS/OS grade might be predictive of positive surgical outcome,” Dr. Mitamura said.

The researchers also noted an increase in the percentage of patients with a normal IS/OS junction seen on OCT after surgery: 47.1% before surgery, 65.7% at 3 months and 75.7% at 6 months. They concluded that presence of a normal IS/OS junction was indicative of functioning photoreceptors, and that the gradual increase in the percentage of patients with a functional junction probably explains the gains in visual acuity over time after surgery that were seen in the study population.

“This correlation between the presence of a normal IS/OS junction and better postoperative visual acuity was probably due to better morphological recovery of the macular photoreceptor cells,” the study authors said.

Whether specific surgical protocols would be beneficial in altering IS/OS recovery after surgery is not clear, Dr. Mitamura said, but the correlation between presence of an IS/OS junction and BCVA in the study results suggest that the timing of surgery may be important.

“I think that … vitrectomy should be performed before the IS/OS becomes absent,” Dr. Mitamura said. “The study in which the natural history of IS/OS status in ERM patients is investigated is needed. Moreover, further studies using spectral-domain OCT are needed to determine a more precise relationship between IS/OS and visual prognosis after ERM surgery.”

Objective measurement

Causes and influences on photoreceptor function are still unknown, but there is growing evidence that early intervention in conditions that may affect this critical area — particularly in disease states that threaten to dislodge the retinal layers — may positively influence outcomes.

“The duration and severity of macular traction by ERM, type of macular edema (especially the presence of foveolar detachment) might be possible risk factors” for IS/OS disruptions, Hyeong Gon Yu, MD, PhD, a co-author of a separate study on IS/OS correlation to visual outcome in ERM, told OSN. “Indocyanine green injection and surgical insult during internal limiting membrane and ERM peeling also may induce the disruption.”

Dr. Yu said his study was not sufficiently powered to look at individual surgical techniques and their role in IS/OS disruption, but it was clear that segment disruption is a potential outcome after ERM repair. The study also showed that segment disruption can have negative consequences on visual acuity.

The next step, according to Dr. Yu, is to verify these findings by using newer spectral-domain OCT devices that can produce a clearer picture of retinal histopathology. A spectral-domain device was installed in Dr. Yu’s team has started a new study on the IS/OS junction in ERM using the new technology.

“Spectral-domain OCT should demonstrate more clearly the macular anatomy and the posttreatment changes in various macular diseases such as macular hole, central serous chorioretinopathy, ERM and macular edema,” Dr. Yu said.

“I think that the functionality of photoreceptor might be useful in evaluating visual function objectively,” Dr. Mitamura said. – by Bryan Bechtel

References:

• Mitamura Y, Hirano K, Baba T, Yamamoto S. Correlation of visual recovery with presence of photoreceptor inner/outer segment junction in optical coherence images after epiretinal membrane surgery. Br J Ophthalmol. 2009;93(2):171-175.
• Suh MH, Seo JM, Park KH, Yu HG. Associations between macular findings by optical coherence tomography and visual outcomes after epiretinal membrane removal. Am J Ophthalmol. 2009;147(3):473-480.

• Yoshinori Mitamura, MD, PhD, can be reached at Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Cho-ku, Chiba 260-8670, Japan; e-mail: ymita@faculty.chiba-u.jp.
• Hyeong Gon Yu, MD, PhD, can be reached at Department of Ophthalmology, Seoul National University College of Medicine, 28, Yeongeon-dong, Chongno-gu, Seoul, 110-744, South Korea; 82-2-2072-2438; fax: 82-2-741-3187; e-mail: hgonyu@snu.ac.kr.