Retina research review - May 2019

May 29, 2019 Dr Narme Deva

Subthreshold nanosecond laser intervention in AMD: the LEAD study

Guymer RH et al.
Ophthalmology. 2018 Sep 20. pii: S0161-6420(18)32135-3.

 

Review: Driven by the need to find an effective intervention in macular degeneration (MD), the laser intervention in early age-related MD (the LEAD) study looked to evaluate the safety of subthreshold nanosecond laser (SNL) treatment in intermediate MD and its efficacy for slowing progression to late AMD. This was a 36-month, multicentre, randomised, sham-controlled trial involving 292 participants with bilateral large drusen and without OCT signs of atrophy. Participants were assigned randomly to receive SNL or sham treatment at six monthly intervals and were observed for any adverse outcome.

Overall progression to late AMD was not slowed significantly with SNL treatment. However, if the presence of reticular pseudodrusen (RPD) at baseline was taken onto account, progression was slowed for the 76% without coexistent RPD at baseline (adjusted HR, 0.23; 95% CI, 0.09-0.59; P = 0.002), whereas an increased progression rate (adjusted HR, 2.56; 95% CI, 0.80-8.18; P = 0.112) was observed for the 24% with RPD. Serious adverse event differences between the groups were not significant.

 

Comment: I have been waiting for the results of this study for several years. SNL treatment has shown promise in a pilot study in intermediate AMD, while laser in drusen treatment has a pretty coloured past in the literature. But with the nanosecond laser we are in completely new territory and much of the evidence backing this is from animal and tissue models. The results of this study are therefore compelling and certainly highlight the importance of considering the different clinical phenotypes in AMD. Ideally, further trials with this laser are needed, but I now suggest that subthreshold nanosecond laser intervention may be helpful for intermediate AMD, excluding the highest risk phenotype of RPD.

 

Vessel density of superficial, intermediate and deep capillary plexuses using OCTA

Lavia st al.

Retina. 39(2):247–258, Feb 2019

 

Review: Optical coherence tomography angiography (OCTA) has allowed visualisation of the retinal capillary plexus in vivo which was not possible with fluorescein angiography. In clinical practice this can be used to quantify non-perfusion in diabetic retinopathy, retinal vein occlusion and many other retinal vascular conditions. The aim of this study was to provide values of retinal vessel density (VD) in the three retinal capillary plexuses (superficial, intermediate and deep), the foveal avascular zone (FAZ) area, and the retinal layer in a cohort of healthy subjects.

OCTA maps of 148 eyes of 84 healthy subjects, aged from 22 to 76 years, were analysed. The relationship between findings and age, sex and image quality was studied. The deep capillary plexus showed the lowest VD, while the mean VD decreased by 0.06% in the superficial vascular plexus, 0.06% in the intermediate capillary plexus and 0.08% in the deep capillary plexus per year. The yearly increase in the FAZ area was 0.003mm² (P < 0.001).

 

Comment: I like this study because it takes a further step in making OCTA a quantitative tool in clinic by documenting a large normative database. VD is a common metric in OCTA studies today, so its necessary to have more reliable data on VD, particularly to accurately assess the deep capillary plexus as its impairment appears to play a critical role in the visual acuity impairment in diabetic maculopathy. Lavia et al suggest the deep capillary plexus is vulnerable to disease processes with lower anatomical VD, and greater diminution with age. The strengths of the study include the large cohort, a good age range and stringent image selection criteria. However, it lacks independent validation and uses slightly different segmentation from other studies.

 

Longitudinal changes in eyes with HCQ retinal toxicity

Allahdina AM et al

Retina. 2019 Mar;39(3):473-484. doi: 10.1097

 

Review: Hydroxychloroquine (HCQ) is often the treatment of choice in many autoimmune diseases and a culprit retinal toxicity. The aim of this study was to characterise functional and structural changes in HCQ retinal toxicity after drug cessation. Twenty-two patients with detected HCQ retinopathy were monitored for six months to 82 months after HCQ cessation with multimodal imaging and visual function tests including visual acuity, Humphrey visual field testing and multifocal electroretinography. Study eyes were categorised into four separate severity stages.

Eyes with detected HCQ retinopathy demonstrated a range of changes following HCQ cessation correlating with retinopathy severity at the time of cessation. Eyes with only subtle and localised retinopathy were mostly stable, whereas more severely affected eyes continued to deteriorate.

 

Comment: These findings highlight the importance of screening for early detection and prompt cessation to preserve good, long-term outcomes. Looking at this study and others, there appears to be a biologic tipping point, which might be disruption of the external limiting membrane observed on OCT, beyond which the retina continues with progressive retinopathy.

 

Dr Narme Deva is a consultant ophthalmologist at Eye Institute, Greenlane Clinical Centre and Retina Specialists in Auckland. She spent several years at Moorfields Eye Hospital in London and holds a Doctorate of Medicine from the University of Auckland for research into ocular wound healing modification.