Inside This Issue 

CLINICAL PEARLS

Selecting the correct patient for Jetrea

By Brad Sutton, OD, FAAO
ORS Fellow and President

Thus far, the adoption of Jetrea (Ocriplasmin) as a routine treatment for symptomatic vitreoretinal adhesion has been somewhat slow in the United States. This may be due, at least in part, to the fact that it was effective roughly one quarter of the time in the original clinical trials, each injection costs approximately $3000.00 to $4000.00 and is covered by some, but not all, insurances, and there have been reports of post injection visual disturbance and visual loss. Currently, post market approval effectivity is being further studied in the ORBIT study. In addition, looking at the results obtained in high volume Jetrea practices over time, certain factors have been identified that improve the success rate to approximately 50%. In other words, by choosing to use Jetrea in patients with certain characteristics, the chance of success is significantly enhanced. These characteristics include……..

1) VMA less than 1500 microns in diameter (focal adhesion rather than broad adhesion) 2) Age less than 65
3) The presence of a full thickness macular hole associated with VMA, if the hole is less than 250 microns in diameter
4) Phakic eyes
5) No ERM

ANSWER TO "YOU MAKE THE DIAGNOSIS"
Derek MacDonald, OD, FAAO
ORS Fellow

This photo represents commotio retina in a 39-year old Caucasian male with a previously uneventful ocular history approximately 18 hours after being hit on the left side of the face by a soccer ball kicked from close range. He reported an immediate and persistent disturbance in the inferior field of the left eye, but denied any central blurring, diplopia, pain, floaters, or photopsia. Entering corrected acuity was 6/6 in both eyes, albeit with an inferior-central ‘smudge’ in the left. Confrontation visual fields were full. Aside from the retinal appearance as noted, including two small peripheral retinal hemorrhages, the balance of the exam, including anterior segment, was normal. At scheduled follow-up in two weeks, the inferior field disturbance had completely resolved. His objective status remained stable with the exception of the expected near-complete resolution of the commotio retinae and associated retinal hemorrhaging. (see photo below).



Vision is typically unaffected in eyes with optic disc melanocytomas; however, decreased visual acuity may occur in some rare cases. Causes for this may include secondary optic neuropathy, optic disc edema, spontaneous tumor necrosis, juxtapapillary or foveal choroidal neovascularization, subretinal fluid from tumor exudation, cystoid retinal edema, retinal traction, epiretinal membrane, central retinal vein occlusion, or, perhaps most concerning, malignant transformation of the tumor.^2,8,9

Commotio retinae is a transient and usually self-limiting whitening of the neuroretina following contrecoup concussive closed-globe injury. , , It was first (and incorrectly) described in the late 1800s as Berlin’s edema when involving the macula. Subsequent histological studies revealed the pathophysiology to involve disruption of the photoreceptor outer segments (OS) and retinal pigment epithelium (RPE), with little retinal edema. , The relatively weak inter-digitation of the photoreceptor OS and RPE seems particularly susceptible to concussive injury, with immediate OS disruption followed by remote RPE phagocytosis of OS material, and potential permanent RPE damage in cases of more severe trauma. Despite blunt trauma being a common cause of visual impairment, the incidence of commotio retinae is unclear, likely due to its typically self-limiting nature.

The advent of spectral domain OCT and adaptive optics has allowed in-vivo confirmation of previous histological observations, and detection of subclinical retinal disruption. , Particularly when the macula is involved, OCT has become an invaluable tool for delineating the extent of outer retinal damage, and in conjunction with presenting visual acuity, aids in predicting the extent of visual recovery.

OCT imaging of mild to moderate commotio retinae typically shows hyper-reflectivity and/or disruption of the photoreceptor inner/outer segment (IS/OS) junction that is often reversible. Defects involving inner retinal structures (including photoreceptor IS and/or external limiting membrane damage, and migration of disorganized RPE toward a degenerating outer nuclear layer) following more significant trauma tend to be permanent, and if central portend poor recovery of visual acuity.

In most cases, including this one, peripheral commotio retinae resolves without sequelae. Significant trauma, however, may cause permanent macular damage not currently amenable to any treatment in up to one-third of patients. Careful assessment of anterior segment, macular, and peripheral retinal integrity at presentation, and diligent lifelong monitoring for remote complications including but not limited to cataract and angle recession glaucoma, are critical components in the care of any patient presenting with a history of blunt ocular trauma.


References
Williams DF, et al. Posterior segment manifestations of ocular trauma. Retina 1990;10:S35-44.
Atmaca LS, et al. Changes in the fundus caused by blunt ocular trauma. Ann Ophthalmol 1993;25:447-52.
Youssri AI, et al. Closed-globe contusion injuries of the posterior segment. Int Ophthalmol Clin 2002;42:79-86.
Berlin R. Zur sogenannten commotio retinae [So-called commotio retinae]. Klin Monatsbl Augenheilkd 1873;1:42-78.
Sipperley JO, et al. Traumatic retinopathy in primates. The explanation of commotio retinae. Arch Ophthalmol 1978;96:2267-73.
Mansour AM, et al. Histopathology of commotio retinae. Retina 1992;12:24-8.
Blanch RJ, et al. Neuroretinal cell death in a murine model of closed globe injury: pathological and functional characterization. Invest Ophthalmol Vis Sci 2012;53:7220-6.
Misko M. Ocular contusion with microhyphema and commotio retinae. Optometry 2012;83:161-6.
Bradley JL, et al. Ultra-high-resolution optical coherence tomographic findings in commotio retinae. Arch Ophthalmol 2011;129:107-8.
Stepien KE, et al. Subclinical photoreceptor disruption in response to severe head trauma. Arch Ophthalmol 2012;130:400-2.
Blanch RJ, et al. Visual outcomes after blunt ocular trauma. Ophthalmology 2013;120:1588-91.
Woo SJ, et al. Optical coherence tomography morphologic grading of macular commotio retinae and its association with anatomic and visual outcomes. Am J Ophthalmol 2013;156:994-1001.
Blanch, RJ (2014) Understanding and preventing visual loss in commotio retinae. Ph.D. thesis, University of Birmingham

Endophthalmitis rate low after anti-VEGF injections

The rate of endophthalmitis after intravitreal anti-VEGF injections is low, although the risk is not entirely eliminated, according to a study in Ophthalmic Surgery, Lasers and Imaging Retina.

The noncomparative consecutive case series assessed the incidence and outcomes of endophthalmitis after intravitreal anti-VEGF injections by reviewing patient records at Bascom Palmer Eye Institute from 2005 to 2014. MarketScan data were used to establish the population-based rate of endophthalmitis for 2011 to 2013.

Approximately one patient per 6,064 injections (0.016%) at Bascom Palmer and one patient per 1,895 injections (0.053%) from the MarketScan database were clinically diagnosed with endophthalmitis. Of the 20 eyes diagnosed at Bascom Palmer, eight occurred after Avastin (bevacizumab, Genentech) injections, six occurred after Lucentis (ranibizumab, Genentech) injections and six occurred after Eylea (aflibercept, Regeneron) injections.

Nine of the 20 cases were culture-positive — five Streptococcus species, three coagulase-negative Staphylococcus species and one non-anthracis Bacillus species — with final visual acuity ranging from 20/40 to no light perception. Final visual acuity for all 20 eyes ranged from 20/25 to no light perception.

AKB-9778 with Lucentis improves central subfield thickness in DME

Patients with diabetic macular edema treated with a combination of AKB-9778 and Lucentis showed a significant reduction in central subfield thickness compared with patients treated with Lucentis alone, according to the Time-2 study results announced in a press release from Aerpio Therapeutics.

The three-armed phase 2a study included 144 patients with diabetic macular edema (DME) who were equally randomized to receive AKB-9778 (15 mg twice daily) as a monotherapy or in combination with Lucentis (ranibizumab, Genentech) therapy compared with Lucentis therapy alone. AKB-9778 is a human protein tyrosine phosphatase beta enzyme inhibitor. The treatment period was 3 months.

The study’s primary endpoint was mean change from baseline in central subfield thickness (CST), and secondary endpoints included visual acuity and safety outcomes.

Patients treated with the combination therapy had a “clinically significant benefit” in reduction of CST compared with patients treated with ranibizumab alone (P = .008), according to the release. As well, there was a positive trend in favor of the combination therapy vs. ranibizumab alone with regard to gaining three or more lines of visual acuity, Aerpio reported in the release.

“Most importantly, the combination approach has the potential to provide better outcomes for DME patients. We are actively planning the next stage of clinical development for this promising compound,” Joseph Gardner, CEO of Aerpio, said in the release.

Quick exposure to hand-held laser device may lead to full-thickness macular hole

Momentary exposure to high-powered hand-held blue-light laser devices was associated with retinal injuries such as full-thickness macular hole, according to a study in the American Journal Of Ophthalmology.

The retrospective case series included 17 eyes of 17 patients with full-thickness macular holes caused by exposure to high-powered hand-held blue-light laser devices. Mean patient age was 18 years (range: 11 years to 30 years).Data were culled from a larger comprehensive study of laser-induced ocular injuries.

Duration of exposure to laser light was less than 1 second. Mean approximate distance from the laser device to the injured eye was 0.95 m. The interval from time of injury to presentation in a hospital ranged from 2 days to 16 months.

The main outcome was macular hole closure; the secondary outcome was final visual acuity. Mean Snellen best corrected visual acuity at presentation was 20/210. Mean macular hole minimum diameter was 351 µm (range: 168 µm to 620 µm).Fourteen eyes underwent 23-gauge pars plana vitrectomy, internal limiting membrane peeling, and gas tamponade (12 eyes) or silicone oil tamponade (two eyes). Mean follow-up after surgical intervention was 7 months.

Eleven of the 14 operated eyes (78.6%) had complete closure of the macular hole. Of the three unoperated eyes, one eye with the smallest macular hole diameter closed spontaneously. Mean final BCVA was 20/62 (range: 20/20 to 4/200.)

Incidence of late AMD quadruples per decade of age in white Americans

The incidence of age-related macular degeneration increased exponentially with age in white American subjects, and women had a higher annual incidence of late AMD compared with men, according to a study in American Journal Of Ophthalmology.

The authors conducted a systematic review and meta-analysis of 74 prospective cohort studies published in Medline, Embase and Web of Science on the incidence and prevalence of AMD in white populations with European ancestry.

Fourteen publications based on 10 population studies contained relevant incidence data and were included for analysis.

The authors culled data on age- and sex-specific incidence of late AMD, geographic atrophy and neovascular AMD, year of study recruitment, AMD grading method and continent.

The annual incidence of late AMD in white Americans age 50 years and older, estimated from prevalence, was 3.5 per 1,000. The incidence was equivalent to 293,000 new cases among white Americans annually.

Annual incidence rates among people age 50 years and older were 1.9 per 1,000 for geographic atrophy and 1.8 per 1,000 for neovascular AMD.

Incidence rates roughly quadrupled per decade of age.The estimated total number of new cases rose rapidly from age 50 years to mid-80s and subsequently began to fall.

Late incidence of AMD was 38% greater among women than among men.

Home monitoring program for high-risk AMD candidates may have public health impact

Broader implementation of a home monitoring program for detecting early AMD in patients at high risk for developing the disease may potentially impact public health in the U.S., according to an analysis presented at the European Society of Ophthalmology in Vienna. Carl D. Regillo, MD, discussed the potential public health impact of the Foresee Home AMD monitoring program, which uses preferential hyperacuity perimetry to help diagnose choroidal neovascularization (CNV) in its earliest stages.

Looking at the data from the AREDS2-HOME study, Regillo and colleagues estimated that, for the high-risk population using the Foresee program in addition to standard of care monitoring who develop CNV, 87% maintain a visual acuity of 20/40 or better, compared with 62% of patients who use only standard of care monitoring. This would result in approximately 101,000 more patients who would maintain vision.

Currently, it is estimated that only 36% of patients have 20/40 or better visual acuity following the initiation of treatment. Applying the results from the HOME study to the U.S. population at risk for developing late age-related macular degeneration (AMD), researchers estimate approximately 205,000 more people would maintain 20/40 or better vision.

These results are applied to estimates of the U.S. population at high risk of developing late AMD to estimate the potential public health effect of home monitoring with the device.

Gevokizumab fails to meet primary endpoint in phase 3 trial for Behçet’s disease uveitis

Xoma today announced gevokizumab failed to meet its primary endpoints in a phase 3 trial in patients with uveitis caused by Behçet’s disease, according to a company press release.

The EYEGUARD-B study — a randomized, double-masked, placebo-controlled study of the efficacy of gevokizumab in the treatment of patients with Behçet’s disease uveitis — enrolled 83 patients with Behçet’s disease uveitis, with 40 patients randomly assigned to receive gevokizumab and 43 patients assigned to receive placebo. The primary endpoint was time to the first acute ocular exacerbation.

“Although the study did not achieve its main objective, we did see signals of drug activity such as preserved visual acuity, less severe ocular exacerbations and a reduced incidence of reported macular edema in patients treated with gevokizumab,” Paul Rubin, MD, senior vice president of research and development and chief medical officer for Xoma, said in the release. “We will continue to work closely with our partner, Servier, and uveitis experts to conduct a thorough analysis of the data to fully understand gevokizumab’s impact on several clinically relevant endpoints.”

Topical squalamine shows encouraging results in phase 2 studies

Final results of the phase 2 IMPACT study of topical squalamine lactate in the treatment of neovascular AMD showed a trend toward increased efficacy in specific lesion types, according to a speaker at the American Society of Retina Specialists meeting .

Squalamine is a small molecule that counteracts multiple growth factors implicated in the angiogenic process, including VEGF and PDGF. The IMPACT study evaluated the effects of OHR-102 (0.2% squalamine lactate ophthalmic solution, Ohr Pharmaceutical) in combination with anti-VEGF in treatment-naïve patients with wet age-related macular degeneration (AMD) and vision between 20/40 and 20/320. Patients recruited across 23 U.S. sites received Lucentis (ranibizumab, Genentech) injection at day zero and then were randomized 1-to-1 to squalamine topical therapy or placebo eye drops administered twice daily. Patients were followed monthly and re-treated with ranibizumab as needed based on strict OCT-guided criteria. The number of re-treatments were similar between the two groups.

The topical therapy was generally well tolerated, it was reported. A phase 3 development program in a targeted population based on complete analysis of the IMPACT study results is under design.