The ARMS2/HTRA1 locus at chromosome 10q26 has been recognized as a major contributor to a genetic predisposition toward AMD. As ARMS2 is considered the most enigmatic of the genes for AMD, a recent study investigated the phenotypic course and spectrum of AMD for the risk haplotype at ARMS2/HTRA1.
Ten studies from the European Eye Epidemiology consortium provided data on 17,204 individuals ages 55 and older. AMD features and macular thickness were determined on multimodal images, and data on genetics and phenotype were harmonized. Risks of AMD features for rs3750486 genotypes at the ARMS2/HTRA1 locus were determined by logistic regression and compared with a genetic risk score of 19 variants at the complement pathway.
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Compared with other genetic variants, the ARMS2/HTRA1 risk variant had a similar phenotypic AMD pattern, but strikingly greater risks of reaching the end stages at earlier ages. Approximately 65 percent of late AMD cases carried the ARMS2/HTRA1 risk allele. ARMS2/HTRA1 risk genotypes weren’t associated with the early manifestations of smaller-sized drusen, which suggests it’s a strong enhancer rather than an initiator of AMD.
Previous studies have pointed out that carriers of the ARMS2/HTRA1 risk haplotype have a strong susceptibility to CNV, reticular pseudodrusen, large drusen, GA progression and more severe visual outcomes, and this study confirmed these findings.
Homozygous carriers were shown to have a three-times higher risk of intermediate AMD, a five-times higher risk of a large macular area covered by drusen and a six-times higher risk of reticular pseudodrusen, compared with noncarriers of the risk variant at ARMS2/HTRA1. Homozygous ARMS2/HTRA1 carriers had a significantly higher risk of reaching end stages—in particular CNV and mixed-late AMD, for which the risk was 13-times higher than for noncarriers. Homozygous carriers had a cumulative lifetime risk of 26.8 percent to develop late AMD, while heterozygous carriers had a risk of 9.4 percent and noncarriers, 4.4 percent.
Not only did carriers have higher risks, age of development of severe stages was also earlier, the authors explained. They found age at late AMD diagnosis to be 9.6 years earlier for homozygous carriers, which is almost twice as early as was reported by others, they say. Correspondingly, these patients had a more-than four-times increased risk of bilateral visual impairment. The risk haplotype at ARMS2/HTRA1 has higher risks of the more severe AMD features than any other single AMD risk variant, investigators say.
Ophthalmology. February 22, 2022. [Epub ahead of print].
Thee EF, Colijn JM, Cougnard-Gregiore A, et al.
Risk Factors for Glaucoma-Surgery Failure
When a glaucoma patient’s progression cannot be checked by medications, SLT and (if appropriate) MIGS, surgeons turn to more invasive, and possibly more effective, alternatives: tubes and trabs. These more powerful interventions are also more fraught with complications. Previous studies have suggested that younger age, male gender, African descent, lower preoperative IOP and neovascular glaucoma are all predictors of tube shunt failure, but there is limited information regarding risk factors associated with surgery failure. Researchers recently sought to identify these risk factors in a pooled analysis of three studies.
A total of 621 patients with glaucoma were enrolled, including 276 patients from the Ahmed Baerveldt Comparison Study, 238 patients from the Ahmed Versus Baerveldt Study and 107 patients from the tube group of the Tube Versus Tra-beculectomy Study.
Younger age was found to be a significant risk factor for tube shunt failure. Younger age is also a risk factor for failure of trabeculectomy surgery, most likely because younger glaucoma patients tend to have higher rates of concomitant secondary or complex glaucoma; are more likely to have had previous surgery and are more likely to be Black, all of which are known risk factors for filtration failure, the authors explained. They suggest that it’s likely younger patients are at higher risk for tube shunt surgery for similar reasons.
Neovascular glaucoma was another risk factor, which has been reported in previous studies. The researchers note that the conjunctiva of patients with the diagnosis of neovascular glaucoma is typically inflamed, with a propensity for extensive postoperative scarring around the implant and subsequent increased resistance across the fibrous capsule. This may lead to both a hypertensive phase in the months following surgery and subsequent surgical failure, they add. Many patients with neovascular glaucoma had markedly elevated IOP and poor visual acuity preop.
Lower preoperative IOP was also strongly associated with surgery failure. The Tube Versus Trabeculectomy Study and the Primary Tube Versus Trabeculectomy Study both found that patients with lower preoperative IOP benefited more from trabeculectomy with mitomycin C than from tube shunt surgery.
“Our study results also suggest that low IOPs are difficult to obtain with tube shunts. The higher failure rate among patients with preoperative IOP less than 21 mmHg was usually because a 20-percent reduction in IOP from baseline was not achieved,” the authors say.
The cumulative probability of tube shunt failure was 38.3 percent at five years. Glaucoma experts have previously said that the tube shunt failure rate is approximately 10 percent per year. The lower failure rate observed in this study may relate to the patient population, the authors suggested.
“It’s noteworthy that nearly half of the patients enrolled in the Tube Versus Trabeculectomy Study had only prior cataract extraction as their qualifying ocular surgery,” the authors note in the paper. “Modifications in implant design may also have contributed to a higher success rate in our study.”
Am J Ophthalmol. February 27, 2022. [Epub ahead of print].
Bowden EC, Choudhury A, Gedde SJ, et al.
Choroidal Thickness and Detachment Repair
Investigators compared the choroidal thickness before and after pars plana vitrectomy for rhegmatogenous retinal detachment repair, as part of a retrospective case series of RRD patients.
Subfoveal choroidal thickness (SFCT) and anatomical success were measured in post-PPV and fellow eyes at presentation, and at three and six months after PPV for RRD repair.
A total of 93 patients (59 percent male) with a mean age of 61.8 ±15.2 years were included. Here are some of the findings:
- Eighty-one patients were anatomically successful (group 1) while 12 re-detached (group 2).
- Mean SFCT of post-PPV eyes at presentation was 258.3 ±82 µm compared with 257.5 ±83.7 µm in fellow eyes (p=0.96).
- Group 2 presented with thicker SFCT than group 1 at baseline (309.2 ±56.2 vs. 250.7 ±82.8 µm; p=0.01).
- Both groups demonstrated a thinning trend throughout follow-up.
- At the six-month follow-up, the mean SFCT was 225.6 ±75.5 µm (p=0.05).
- Fellow eye SFCT was stable throughout follow-up (257 ±83.7 at baseline vs. 255 ±80.2 µm at six months).
Investigators report that eyes with rhegmatogenous retinal detachment demonstrated thinning in the subfoveal choroidal thickness after vitrectomy surgery. Given that eyes with recurrent retinal detachment presented with thicker choroids at baseline, researchers suggest that thicker SFCT at presentation may play a role in retinal redetachment.
Retina 2022; Feb 25, 2022. [Epub ahead of print].
Trivizki O, Eremenko R, Au A, et al.
The Importance of Stereopsis For Quality of Life
Vision-related quality of life is influenced by more factors than acuity alone, and stereopsis in particular is an important but underrepresented element, according to a recently published study that assessed this relationship in patients with branch retinal vein occlusion (BRVO). The prospective, multicenter study included 37 patients with BRVO receiving intravitreal ranibizumab and 24 age-matched controls.
The researchers report that intravitreal ranibizumab significantly reduced central foveal thickness and improved stereopsis scores from two to 12 months. They also note that, compared with controls, BRVO patients had significantly worse stereopsis before and after receiving injections. Treatment led to significantly improved visual function scores (NEI visual function questionnaire). The researchers note that baseline TNO stereotest score was associated with vision-related quality of life in BRVO patients.
They add that clinicians should pay attention to stereopsis as well as visual acuity in BRVO patients, due to quality-of-life considerations. They say that reduced stereopsis induced by retinal diseases is improved with adequate therapy, citing previous studies that demonstrated significant stereopsis improvements after vitrectomy for epiretinal membrane and macular hole. Six-month intravitreal ranibizumab treatment has been proven to be effective for BCVA, stereopsis and contrast sensitivity in patients with BRVO, they note. However, they add that another study reported that intravitreal ranibizumab didn’t improve metamorphopsia.
BMJ Open Ophthalmol. March 3, 2022. [Epub ahead of print].
Morikawa S, Okamoto F, Murakami T, et al.
