This article was reviewed by J. Fernando Arevalo, MD



The new 248-gene panel provides definitive diagnoses and more personalized care for patients who previously were thought to be negative for an inherited retinal disease (IRD) using a 31-gene panel.

Gene therapy is in its infancy, and it was only in 2017 that a major clinical breakthrough became available with the launch of voretigene neparvovec-rzyl (Luxturna, Spark Therapeutics Inc), which can be used to treat IRDs caused by biallelic mutations in the 

Exploring novel gene therapy approaches to treat ocular disease

“With this therapy and other such therapies on the horizon, it is becoming increasingly important to obtain molecular diagnostics for patients with suspected IRDs,” said Mark Seraly, MD, a resident at the West Virginia University School of Medicine in Morgantown, West Virginia.

Dr. Seraly and associates conducted a retrospective chart review to determine the usefulness of the new 248-gene panel compared with the 31-gene panel for providing molecular diagnoses in 46 patients (50% men; average age, 48 years) from June 1, 2019, to October 31, 2019. 

The patients underwent next-generation sequencing with the expanded panel of 248 genes.

Blood or saliva samples were obtained during patient visits. The investigators reviewed the visual acuity, imaging results, electroretinography results, family history, and previous genetic results. 

As needed, patients were encouraged to consult a genetic counselor and arrange for variant testing, Seraly said.



Seraly reported that 13 (28.2%) of the 46 patients had positive molecular diagnoses of their IRDs; 12 (26.1%) patients were found to be carriers of pathogenic genes associated with IRDs. These 2 patient groups were urged to undergo additional genetic counseling and variant testing.

Twenty (46.5%) patients had variants of unknown significance, which means that the association between the genetic alterations and the IRDs is not fully understood, he said. Finally, only 1 (2.2%) patient in our cohort had no detected mutations.



 Intravitreal gene therapy holds promise for novel wet AMD treatment

In contrast, 18 (39.1%) patients from this cohort had undergone genetic testing 1 year prior using the 31-gene panel, and the results were negative for an IRD.

“That panel either yielded no identifiable mutations or only those of unknown significance,” Seraly said.

When the same patients underwent retesting with the 248-gene panel, the results differed substantially, with 9 (50%) of individuals gaining new clinically relevant genetic information. 

Five patients received an unequivocal molecular diagnosis and the other four were found to be carriers of single pathogenic mutations. 

The remaining 9 of 18 were all found to have additional variants of unknown significance, as compared to their prior genetic results, Seraly said.

“The new gene panel provided a wealth of information that facilitated definitive diagnoses for 5 patients with syndromic IRDs,” he said. These diseases included 2 patients with Bardet-Biedl syndrome, 2 with Usher syndrome, and 1 with Cohen syndrome.


Intravitreally injected hRPCs improve vision in retinitis pigmentosa cases

In the same cohort, 4 patients had autosomal-dominant IRDs, and 1 patient had x-linked retinitis pigmentosa. Seraly pointed out, however, that despite these diagnoses, the panel did not include analysis of the 

 gene, and some patients may have been overlooked.

Three patients in the cohort went on to familial variant testing.



A 10-year-old girl presented with frequent headaches and distorted vision, however, her visual acuity was 20/20 in both eyes. Slit-lamp examination of the anterior chambers was unremarkable. 

However, color fundus photos of both eyes showed pale-yellow lesions located inferotemporal and temporal to the macula. 

Fluorescein angiography showed that these lesions were hyperfluorescent in the late arteriovenous filling phases. Incomplete retinal vascularization was seen in the temporal peripheral retinas in both eyes.

 showed normal macular architecture in the right and left eyes; however, inner retinal folds were visibly associated with an epiretinal membrane in the right eye and an inner retinal tuft in the left eye that was associated with an epiretinal membrane and several small areas of underlying photoreceptor dropout.


Stem cells for dry AMD with GA show promise in early study

This patient underwent genetic testing and was shown to have a heterozygous mutation in the 

 gene on exon 2. Testing of the family showed 4 individuals with similar mutations in the same gene. The patient was diagnosed with autosomal-dominant familial exudative vitreoretinopathy.

“This information allowed us to tailor our follow-up with the patient in clinic and our referral for IRD resources,” Seraly said.

Based on their experience with the 248-gene panel, the investigators concluded that the expanded panel facilitates more personalized patient care—that is, genetic counseling and familial variant testing. The panel also allows refinement of searches for support groups and low-vision resources, and searches for prospective clinical trials in the future.

Seraly concluded that the current study revealed that the majority of patients were only found to harbor variants of unknown significance, indicating that more research is needed to better understand the relationship between a patient’s genotype and the phenotypic expression of their IRDs.

“In addition, in patients who received equivocal results from prior genetic testing, the 248-gene panel provided 50% of patients with new clinically relevant information about their pathogenic mutations,” he said. “More extensive panels may detect larger numbers of IRDs.”


Seraly has no financial interest in this subject matter.

Articles

Investigators reviewed visual acuity, multi-modal retinal imaging, electroretinography, family history.


Gene panel offers expanded diagnostic capability of inherited retinal diseases

pandemic, our practice was closed from the end of March through April to everyone except patients with emergent conditions. 

During this time, I quickly ramped up telemedicine visits for almost all cases that I handled, “seeing” approximately 100 patients.

Thanks to the Centers for Medicare & Medicaid Services relaxing telemedicine regulations and Health Insurance Portability and Accountability Act rules, I was able to use Zoom, FaceTime, and even Facebook Messenger—whatever the patient was most comfortable with—for my virtual consultations, most with patients suffering from acute

exacerbations such as blepharitis, meibomian gland dysfunction (MGD)–associated conjunctivitis, contact lens–related red eye, lid disease, severe allergies, and ocular rosacea. 

Amid pandemic, friendly bugs can help protect the eye from infection

In the absence of a slit-lamp examination to diagnose these acute OSD patients, I found that treating with tobramycin 0.3%/dexamethasone 0.05% ophthalmic suspension (Tobradex ST; Eyevance Pharmaceuticals) allowed me to cover all the bases for conditions that typically involve mixed mechanisms. 

The product contains the antibiotic tobramycin combined with a reduced concentration of dexamethasone, compared with the standard version, which has twice the concentration of anti-inflammatory agent (0.1%). In addition, Tobradex ST has a higher viscosity on the ocular surface, which leads to increased retention time and improved bactericidal activity.1

The drop’s novel xanthan gum delivery technology, termed XanGen by the company, enhances ocular surface retention. 

I use tobramycin 0.3%/dexamethasone 0.05% ophthalmic suspension as a bit of a “catch all” product. I am finding it especially beneficial when it comes to confidently treating OSD patients via telemedicine. 



Spotlighting telemedicine in the year of a pandemic



Clinical investigations into the pharmacokinetics of the ST formulation have found that ocular tissue concentrations of tobramycin were up to 12.5-fold greater with Tobradex ST compared to original Tobradex.

 

At 10 minutes postinstillation, the concentration of tobramycin in the tear film was about 8 times higher for ST compared to the original agent.


Screen time is up. Patients are spending more time at home as a result of the pandemic and as an increasing number of offices make working remotely a permanent arrangement. 

For patients with chronic ocular surface conditions, including dry eye, MGD, or blepharitis, this increase in screen time can lead to worsening of redness, burning, and irritated eyes. Patients wind up turning to self-treatment.

This is where tobramycin 0.3%/dexamethasone 0.05% ophthalmic suspension fits in, not as a long-term therapy, but rather for addressing acute exacerbation, calming inflammation, and treating disease. 



Novel dexamethasone formulation shows efficacy and safety with once-daily use



Patients may develop blepharoconjunctivitis from chronic computer use, subsequently inhibiting their ability to work or making it difficult to just keep their eyes open. 

Compounded by the cosmetic problem of having bloodshot eyes when they need to be on professional Zoom calls, patients can have a true emergency for which they need fast relief.

The combination tobramycin-dexamethasone drop in the ST formula is appropriate for acute exacerbations from a broad category of ocular surface diseases. 

This includes situations like inflamed exposure dry eye as a result of staring at the computer or inflammation associated with blepharitis, MGD, or ocular rosacea.


Because the COVID-19 environment is our new reality, telemedicine will only increase in importance for our patients and our practices. 

In this setting, the safety and efficacy of the agents we prescribe are even more crucial. Tobramycin 0.3%/dexamethasone 0.05% ophthalmic suspension is indicated for steroid-responsive inflammatory ocular conditions in which a corticosteroid is appropriate and superficial bacterial ocular infection or a risk of bacterial ocular infection exists. 


Pearls for practicing in the COVID-19 era



Moreover, the ST formulation uses pharmaceutical-grade xanthan gum to stabilize the combination and allow greater delivery and ocular surface retention of tobramycin and dexamethasone. 

The adverse effect profile is also very favorable. 



p: 314/966-5000 e:ranjanmalhotramd@gmail.com


Malhotra is in private practice at Ophthalmology Associates, Cornea and LaserVision Institute, St. Louis, Missouri. He is a consultant to Eyevance.


1. Scoper SV, Kabat AG, Owen GR, et al. Ocular distribution, bactericidal activity and settling characteristics of TobraDex ST ophthalmic suspension compared with TobraDex ophthalmic suspension. 

. 2008;25(2):77-88. doi:10.1007/s12325-008-0019-9

2. Torkildsen GL, Cockrum P, Meier E, Hammonds WM, Silverstein B, Silverstein S. Evaluation of clinical efficacy and safety of tobramycin/dexamethasone ophthalmic suspension 0.3%/0.05% compared to azithromycin ophthalmic solution 1% in the treatment of moderate to severe acute blepharitis/blepharoconjunctivitis. Curr Med Res Opin. 2011;27(1):171-178. doi:10.1185/03007995.2010.539603

Antibiotic-steroid combination boosts confidence with delivery

This article was reviewed by Jeremiah Brown Jr, MD, MS



A contemporary look at treatment patterns for proliferative 

 (PDR) shows that the vast majority of patients with PDR will receive an anti-VEGF injection regardless of whether they have 

), said Jeremiah Brown Jr, MD, MS, at the 2020 virtual meeting of the American Society of Retina Specialists.

Brown presented the findings from a retrospective review conducted using data from the American Academy of Ophthalmology’s Intelligent Research in Sight (IRIS) registry, the nation’s first comprehensive eye disease clinical registry.



Researchers advocate for intraoperative intravitreal steroid during cataract surgery in DME eyes

The study included 33,452 patients with PDR and new onset vitreous hemorrhage treated within 3 months who had a visit between June 2017 and June 2018.

Eighty percent of patients had a diagnosis of DME, and 84% of those patients received anti-VEGF treatment. However, 69% of patients with PDR alone also were given anti-VEGF therapy. 

In addition, anti-VEGF treatment was received by approximately one-half of patients who underwent panretinal photocoagulation (PRP) or vitrectomy if they also had DME, and by approximately one-third of those without DME who were treated with PRP or vitrectomy.




“The data from this study show that treatment patterns for PDR have undergone a dramatic shift since the advent of anti-VEGF medications,” said Brown, who is in private practice at the Brown Retina Institute in San Antonio, Texas. “Ophthalmologists are no longer relying on a foundation of repetitive peripheral laser applications to treat PDR but instead are taking care of patients using anindividualized mix of anti-VEGF injections, PRP, and vitrectomy.”

Brown also pointed out that the “research also highlights the enormous value of the IRIS registry, which contains information from hundreds of thousands of patient visits, for enabling us to look into our practices and evaluate trends to improve patient care.”



Clinical trial outcomes for macular edema don’t translate to ‘real-world’ settings

Providing context for undertaking the study, Brown noted there are some clear indications for treating DME with anti-VEGF medications, while the timing and the need for their use in the treatment of PDR are less clear.




“Our treatment for PDR was built on the foundation of the diabetic retinopathy study published in 1976 that established peripheral scatter laser photocoagulation as the standard of care,” he said. “More recently, Protocol S [NCT01489189] and the Clarity study showed similar visual outcomes could be achieved with anti-VEGF therapy. Our study sought to understand how the available options are being employed in the real world.”

Data on the use of PRP and vitrectomy showed that in the cohort of patients with PDR and DME, 30% were treated with PRP, 17% received PRP plus an anti-VEGF medication, and 20% underwent vitrectomy, of which approximately one-half also received an anti-VEGF injection.



Managing the challenge of cataract surgery in eyes with diabetic macular edema

Among those patients who had PDR without DME, 35% received PRP, while 11% received PRP plus anti-VEGF injection, and 29% underwent vitrectomy, of which 36% of those also received anti-VEGF therapy.



The study also analyzed visual acuity (VA) outcomes at 6 months following treatment, and the results showed that the percentage of patients achieving logMAR VA of 0.4 or better (approximately Snellen 20/50) was similar regardless of whether they received an anti-VEGF injection. Percentages of patients achieving logMAR VA of 0.4 or better were 59% in the anti-VEGF cohort, 65% among those treated with PRP alone, and 63% for patients who received both treatments.

Considering patients undergoing vitrectomy, approximately 50% achieved logMAR VA of 0.4 or better whether they had surgery alone or combined with anti-VEGF treatment.



Identifying biomarkers to predict diabetic retinopathy progression


Brown concluded that it is interesting to see that the VA results are similar with or without anti-VEGF therapy “if we consider that retina specialists would be more likely to use an anti-VEGF agent in patients with more severe proliferative disease, more severe vitreous hemorrhage, or more ischemic appearing retinas, along with the fact that patients with longstanding DME may reach a plateau in their VA improvement because of foveal atrophy or persistent edema.”

“Therefore, it is encouraging to note that patients treated with anti-VEGF injections were able to achieve the same level of vision as the patients treated with PRP or vitrectomy alone who likely had milder hemorrhage,” he said. 



Brown serves as an investigator, consultant, or member of speakers bureau for companies that market or are developing treatments for diabetic eye disease.

DME diagnosis plays no role in determining whether patients will receive injection.

Probe of IRIS registry: Anti-VEGF injections key treatment for PDR


This article was reviewed by Madeline Hay



Elevated IOP after cataract surgery is the most frequent complication postoperatively and can lead to irreversible optic nerve damage and vision loss if not treated.

There remains a question, however, about the utility of using preoperative IOP as a predictor of IOP the day after cataract surgery in patients without glaucoma and ocular hypertension (OHT).

Although the long-term effect of cataract surgery is decreased IOP, a transient elevation of IOP is the most common complication in the days after 

 and it can require treatment intervention, according to Madeline Hay, a third-year medical student at the Western University of Health Sciences, College of Osteopathic Medicine, Pomona, California.


Improving surgical safety, efficiency, and outcomes for patients

Hay and her colleagues wanted to determine how preoperative IOP relates to the IOP on the first day after an uncomplicated cataract surgery with IOL implantation in patients without glaucoma or OHT.

The investigators conducted a retrospective analysis of IOL implantation surgical data between January 1, 2016, and June 1, 2018, in patients older than 60 years who did not have glaucoma, OHT, pseudoexfoliation syndrome or pigment dispersion syndrome; the study also excluded patients whohad a history of IOP elevation in response to steroids, poorly dilating pupil, ocular trauma, or current use of IOP-lowering eyedrops. 

The IOP was measured preoperatively and postoperatively within 16 to 30 hours after surgery.

Topical moxifloxacin: Best choice before cataract surgery?


The investigators reported that 288 eyes were included; 56.9% of patients were women and the average patient age was 73.4 years. The average preoperative IOP was 15.98 mm Hg compared with the average IOP on day 1 postoperatively of 19.47 mm Hg. 

Results indicated that the preoperative IOP was a significant (P < 0.0001) predictor of the IOP 1 day after surgery. 

Hay concluded that elevated preoperative IOP was associated with 1-day postoperative IOP elevations in patients without glaucoma or ocular hypertension following uncomplicated cataract surgery.

“This knowledge may help clinicians to identify patients at significantly increased risk for IOP-related complications,” she said. “Accordingly, this provides meaningful evidence in support of prophylactic preoperative treatment in high-risk patients to prevent loss of vision due to postoperative IOP elevations.”



Hay has no financial interest in this subject matter.

Elevated pressure can lead to irreversible optic nerve damage, vision loss

Pre-operative IOP hints after cataract surgery

Aproved for use in Europe, the small-aperture IOL IC-8 (AcuFocus) is proving to be a very useful implant, particularly for patients who are not good candidates for current multifocal (MF), accommodating or extended depth-of-focus technology. 

The small aperture lens approach to vision correction is based on pinhole optics – a novel property not found in other available lenses.

The pinhole optic blocks out-of-focus, stray light, thereby creating a depth of focus with the small aperture of 1.36 mm allowing for a continuum of vision. 



Aspheric, aberration-free IOL leverages technology for performance


The lens is forgiving, with a broad landing zone that makes it virtually immune to up to 1.50 D of astigmatism, while at the same time offering high-quality, sharp vision and less concern with photic phenomena.

The IC-8 is a single-piece, hydrophobic acrylic IOL embedded with an opaque mini-ring. Besides Europe, it is also approved for use in Asia and is currently being investigated in clinical trials in the United States. 

A retrospective comparative review of studies assessed the range and quality of vision with small-aperture, accommodating or MF 

The IC-8 IOL was found to enhance vision at all distances, with improved visual acuities and a broad range of continuous functional vision. 

Likewise, the patients receiving this implant experienced excellent intermediate vision and binocular mesopic contrast sensitivity, which is comparable to the other lenses.



Getting it right: There is no magic bullet for IOL calculations


The small-aperture IOL was paired with an aspheric monofocal IOL and compared with bilateral implantation of the MF lens Acrysof ReSTOR +3.00 D (Alcon) and MF IOL Tecnis +4.00 D (Johnson & Johnson Vision), and with the accommodative Crystalens AO (Bausch + Lomb).

The IC-8 cohort comprised 105 patients, with the Restor, Tecnis and Crystalens platforms implanted into 25, 22 and 26 study subjects, respectively.

Investigators examined 6-month postoperative monocular uncorrected and distance-corrected vision at distance (4 m for IC-8, 6 m for others), intermediate (67 cm for IC-8, 80 cm for others) and near visual acuities (all 40 cm). 

They looked at defocus curves (binocular for IC-8, monocular for others) and compared binocular mesopic contrast sensitivity with and without glare.



ASCRS 2020: Assessing aberration of monofocal toric IOL with enhanced optic recovery, alignment


The defocus curves revealed that the small-aperture lens had a 4.50 D continuous expanse of vision compared with 4.50 D for Restor, 4.00 D for Tecnis and 2.50 D for Crystalens – but the two light-splitting lenses were not continuous. 

Rather, they showed a dip in the middle range for intermediate vision of patients.

All four IOL groups had a similar mean uncorrected distance visual acuity (0.02–0.11). The small-aperture lens and Crystalens had a mean uncorrected intermediate visual acuity of 0.08 and 0.07. This was almost a 2-line improvement over Restor and Tecnis (0.24, P<0.0001).



Pinhole camera effect in small-aperture implant corrects presbyopia in patients​ 



Unwanted visual effects such as blurring, fluctuating vision and ghosting were of low severity in all the lenses studied, with a very low ghosting score for the IC-8 lens. 

Along with the Crystalens, the small-aperture IOL elicited very few reports of halos when both were compared with the two MF lenses, which received higher scores for halo and glare. 

With regards to the contrast sensitivity that patients experienced, the lenses were binocularly comparable.

The small-aperture lens group was worse than Crystalens at 6 cycles per degree (cpd), but better than Tecnis at 3 cpd, and with no glare (P<0.05 ).



Trifocal IOL a key for premium cataract surgery practice


When compared with accommodating or MF IOLs, the IC-8 IOL enhanced vision at all distances and provided both improved visual acuities and a broad range of continuous functional vision. 

Likewise, the patients receiving this lens experienced excellent intermediate vision and binocular mesopic contrast sensitivity comparable to the other lenses.

The IOL has minimal impact on the ability to visualise the retina with optical coherence tomography or on visual fields. One study recently showed that even with bilateral implantation, patients experience a minimal change in contrast.

Changing focus of accommodating IOLs now reaching a new level


Moreover, the expanded depth of focus with the small-aperture lens allows refractive surgeons to target roughly -0.75 D without really losing much distance.

The IC-8 lens proved tolerant of up to 1.00 D deviation from the refractive target and it corrects up to 1.50 D of corneal astigmatism free from the concerns that accompany toric technology. One should remember that every degree of rotation is about a 3.3% reduction in the offset of the astigmatism.

In addition, toric lenses do not come in every power. Even just 0.75 D of residual astigmatism has a significant impact on MF lens performance at all distances.


The IC-8 IOL should prove particularly useful for patients with previous refractive surgery or highly aberrated corneas, extending to those with irregular astigmatism from trauma, a small iris defect or in patients with a pupil that is not completely round. 

Also, in eyes with a high angle kappa, the central ray can traverse the central ring and adversely affect the performance of multifocal IOLs, whereas the implant will not be impacted and should be a ‘shoo-in’.



Finding an option with presbyopia-correcting IOLs​ 


For those patients who are not good candidates for other premium technology, the IC-8 lens gives surgeons something unique to offer. 

This IOL is forgiving in terms of hitting both targets, sphere and cylinder with a broad landing zone; has a very low dysphotopsia rate; and results in high patient satisfaction. 

In fact, 95% of small-aperture patients reported that they would undergo the procedure again. 




Pepose is a professor of clinical ophthalmology at Washington University’s School of Medicine, United States, and director of the Pepose Vision Institute in St. Louis, Missouri. Dr Pepose is an investigator for the IC-8 IOL clinical study.

---


1. Ang RE. Visual performance of a small-aperture intraocular lens: first comparison of results after contralateral and bilateral implantation. J

2020;36:12-19.
2. Novis C. Astigmatism and toric intraocular lenses. 

Optics block out-of-focus and stray light, allow continuum of vision.


Small-aperture single-piece IOL could fill unmet need in patients

Reviewed by Logan T. Vander Woude, DO, MPH

Aretinal implant (Argus II Retinal Prosthesis System, Second Sight) designed to provide prosthetic vision to patients blinded by retinitis pigmentosa significantly improves quality of life.

Although the implant is not a replacement for normal vision, it allows patients to recognize shapes and better distinguish between light and dark.


Retinal pathologies challenging to image with current technologies

“It is almost like having a sixth sense, but the patients have to be trained in the use of the device,” according to Logan T. Vander Woude, DO, MPH, of the University of Florida (UF) College of Medicine in Gainesville.

The device works by using an external camera that relays visual input signals to a surgically implanted microarray on the macula, which stimulates the inner retinal layers that send these signals to the optic nerve.

An issue with evaluating vision after the implantation of a retinal implant is that it is challenging to assess the vision the device provides using standard measurements. 

This led Vander Woude, together with Ramak Roohipourmoallai, MD, and Gibran S. Khurshid, MD, FRCS, FRANZCO, FACS, both vitreoretinal surgeons at UF College of Medicine, to conduct a study using the Visual Function Questionnaire (VFQ-25) to assess the impact the machine-generated vision has on patients’ quality of life before and after implantation of the device.




Seventeen patients (mean age, 57 years) completed the VFQ-25 before the device was implanted and again after implantation and completion of training. All patients qualified for retinal implantation with light perception or no light perception vision in both eyes.

The questions measured the effect of having prosthetic vision on the patients’ lives, including their social well-being and dependence on activities of daily living. 

In addition, another 13 questions were included to assess the quality of life to a greater degree than the questionnaire could shed light on, Vander Woude explained.

The analysis indicated that each overall category improved significantly after implantation of the Argus II, including overall health and vision (

 < .0001), difficulties with activities (

 < .0002), and response to vision problems (

“This included improved perception of vision (

 < .001). 

Patients also stated they could accomplish more tasks during the day (

 < .001) and were less dependent on others (

Persistent retinal detachment related to retinoblastoma

In addition, the 13 supplemental questions addressed the daily living activities that were not well addressed by the VFQ-25, which included writing checks, reading small print, recognizing friends and family, and engaging in outside activities alone. 

Those results reflected the patients’ subjective improvement in general vision (

 = .03), and limitation in their daily activities (

It is important to note that eye pain, discomfort, worry about eyesight, frustration, and embarrassment about questions were not significantly different before or after the implantation of the retinal device, meaning there were no negative impacts on the patients’ lives.

Vander Woude concluded that although retinal implant is not an exact replacement for natural sight, it allows patients to recognize shapes and perceive the contrast between light and dark objects.

“Based on the survey results, the patients’ overall quality of blind life significantly improved after Argus II implantation, including the activities of daily living and social well-being, such as the ability to match clothes,” he said. “The scores in all 3 broad categories of the VFQ-25 improved, as well as several individual factors. Importantly, there were also no negative impacts on the patients’ quality of life.”



Logan Vander Woude, DO, MPH, is a fourth-year resident in the Department of Ophthalmology at the University of Florida College of Medicine in Gainesville. He has no financial interest in this subject matter.

Device allows visually impaired to recognize shapes, distinguish between light and dark.


Retinal implant improves quality of life in patients with RP


This article was reviewed by Andrea Blitzer, MD


 may be another benefit of metformin for protecting against age-related diseases, according to a case-control study undertaken by a team of investigators at the University of Chicago.

Led by Dimitra Skondra, MD, PhD, an associate professor in the Department of Ophthalmology and Visual Science, the research analyzed 10 years of data from the IBM MarketScan Commercial and Medicare Supplemental databases. 





It found that the strongest effect occurred at low to moderate doses of metformin, was not restricted to patients with diabetes, but was not present among patients with diabetes who had diabetic retinopathy.

Andrea Blitzer, MD, a member of Skondra’s team and an ophthalmology resident at the University of Chicago, presented the findings at the Association for Research in Vision and Ophthalmology 2020 virtual annual meeting.

“Further studies are needed to confirm the protective benefit that we identified for metformin and to investigate the underlying pathways,” she said. “If our findings are confirmed in clinical trials, the research may lead to a novel therapeutic strategy for this blinding disease.”

Easing patient comfort, pain perception of intravitreal injections​ 




Previous studies found that metformin reduced the incidence of diabetes mellitus, diabetes-related mortality, cardiovascular diseases, cancer, dementia, and all-cause mortality. It has also been reported to reduce the risk of glaucoma.

“Metformin targets mediators and pathways that affect inflammation, cell survival, stress defense, oxidative stress,” Blitzer said. “All of these can play a role in health span and longevity, and a number of the pathways and mediators that are targets for metformin have also been implicated in the pathogenesis of AMD.”

Blitzer noted that these details led to Skondra’s study investigating whether metformin decreases the risk of developing AMD using a big data approach.


Contrast sensitivity shows potential for measuring visual function loss in early AMD


The cases and controls for the research were identified through a search of the MarketScan database for the years 2008 to 2017. The study looked at people 55 years of age or older who had newly diagnosed AMD.

A control subject was selected for each case from among a pool of 31 million patients and matched by age, comorbidities, and region of the United States. The investigators were able to determine metformin usage based on claims data.

The study looked at a total of 312,404 cases that were then matched with controls. Compared with the controls, patients with AMD were more likely to smoke, to have hyperlipidemia, and to have diabetic retinopathy.

In a multivariate model adjusting for risk factors and other medications, the use of metformin significantly decreased the risk of being newly diagnosed with AMD within 2 years by 6%. 



Deep learning algorithm proving accurate for AMD classification



With stratification by metformin dose, patients who had received low to moderate doses had the greatest risk reduction (9% and 10%, respectively).

Because metformin is primarily used as an antihyperglycemic drug, the investigators also analyzed the data to see if the potential protective effect of metformin on AMD development occurred only in the cohort of patients with diabetes. They found that the protective effect was similar in the diabetic cohort as in the overall cohort.

With cases more likely than controls to have diabetic retinopathy, another analysis considered if the presence of this ocular complication of diabetes was an important factor for metformin’s risk reduction. The benefit of metformin only occurred in the absence of diabetic retinopathy, the team reported.

Finally, a protective benefit of other antihyperglycemic medications and statins was investigated. 



Vision-related quality of life: Impacts of advanced AMD


In multivariate models, other diabetic medications seemed to have a mild protective effect as well, but metformin remained protective even in multivariate analysis adjusting for the effects of other medications

“Metformin is a well tolerated and is the most commonly used oral medication to treat diabetes,” Skondra concluded. “The findings from our team may uncover a role for its use as a possible therapeutic intervention for AMD as well.” 



Skondra has no relevant financial interests to report.


Blitzer has no relevant financial interests to report.

Research could lead to a novel therapeutic strategy for blinding disease 

Antihyperglycemic drug linked to reduced risk of new onset AMD

This article was reviewed by Victor H. Gonzalez, MD



The fluocinolone acetonide intravitreal implant (Iluvien, Alimera Sciences), which treats diabetic macular edema (DME), showed significant decreases in the mean central subfield thickness (CST) from baseline, along with improved or stabilized visual acuity (VA), according to the 2-year results of an ongoing study.

The interim analysis of PALADIN, a phase 4 prospective observational study (NCT02424019), included 115 eyes (95 patients; mean age, 67 years) with DME (mean duration, 4.7 years; range, 1-13) treated with the fluocinolone implant at 0.2 µg/day. 





The patients were evaluated on day 1, week 1, and month 2 after implantation and then quarterly from months 3 through 24. The VA was stratified by 20/40 or better (n = 39) and worse than 20/40 (n = 76). 

The best-corrected visual acuity (BCVA), central foveal thickness (CST), and IOP were recorded at baseline and after treatment. 

Data from up to 36 months of previous treatments, as well as VA and CST, also were collected, according to Victor H. Gonzalez, MD, who is in private practice in McAllen, Texas.



Stabilized or improved vision with implant


All patients had undergone previous treatments for DME, and regardless of VA, all had a progressive decrease in BCVA over 24 months before treatment with the fluocinolone implant. In the group with VA of 20/40 or better, the baseline mean BCVA was 76.9 letters; in the group with VA worse than 20/40, 53.4 letters.


During the 2 years before study enrollment, most patients had received fewer than 4 injections, indicating significant undertreatment, Gonzalez said.

At month 24 following treatment with the implant, the group with VA of at least 20/40 and the group with the worse VA had BCVA increases to 77.8 letters and 56.4 letters respectively, or the VA was stable, according to Gonzalez.

“The treatment stabilized or improved the vision, with most of the patients receiving [fewer] than 4 injections during the 2-year follow-up period,” he said. Most patients did not require rescue therapy for at least 1 year.


Bowtie artifacts: Clinical biomarkers for center-Involving DME?

After implantation, the mean CST dropped significantly from day 7 (

 < .001) and remained decreased for all time points out to month 24 (

 < .001). 

The decreases in CST appeared more consistent with the continuous treatment provided by the implant compared with before study enrollment; 42.2% of patients had a CST of 300 µm or less at 2 years compared with 33.6% at baseline.

The mean IOP did not vary substantially after patients received the implant. Any IOP elevation was managed with topical medications.

Gonzalez noted that in most patients, sustained continuous release of fluocinolone led to a significant reduction in the mean CST from the baseline value to month 24 after implantation.



Subthreshold laser may reduce intravitreal injections for DME


“We saw an increased percentage of eyes with CST of 300 µm or less at month 24,” he concluded. “As a result, the vision either stabilized or improved with 1 or fewer additional treatment annually in most patients. There was a patient-friendly treatment shift, with more than 50% of patients receiving [no more than 1] treatment annually to achieve the reported gains in vision. The IOP profile was predictable and manageable in all patients.”



Gonzalez is a paid consultant to and receives research support from Alimera Sciences.

Study examines use of fluocinolone acetonide for treating DME in patients.


Intravitreal implant offers anatomic, visual improvement

This article was reviewed by Dennis M. Marcus, MD



Patients achieved substantial visual gains following vitrectomy without endolaser combined with aflibercept (Eylea, Regeneron Pharmaceuticals) to treat vitreous hemorrhages (VHs) associated with proliferative diabetic retinopathy (PDR), according to the results of the LASERLESS trial (NCT02976012).

Anti-vascular endothelial growth factor (VEGF) therapy is an effective treatment for PDR in less complicated eyes that do not require vitrectomy. 



Probe of IRIS Registry shows anti-VEGF injections leading treatment for PDR



The 5-year results of the Protocol S study with ranibizumab (Lucentis, Genentech; NCT01489189) compared with panretinal photocoagulation (PRP) for PDR not requiring pars plana vitrectomy showed that vitrectomy with endolaser resulted in large losses of visual fields and significantly decreased visual field point scores. 

In addition, the CLARITY study (ISRCTN32207582) showed that aflibercept was noninferior to PRP for PDR and achieved better visual acuity (VA) levels and less visual field loss.

“Thus, anti-VEGF therapy is a viable alternative to endolaser for PDR-related vitreous hemorrhages,” according to Dennis M. Marcus, MD, who is in private practice in Augusta, Georgia.



Saving memories: Do anti-VEGF agents contribute to cognitive loss?


Marcus presented the 2-year results of LASERLESS, a phase 1/2 prospective, randomly assignedinterventional study of the safety and efficacy of endolaserless vitrectomy in which preoperative, intraoperative, and postoperative intravitreal injections of aflibercept were administered in eyes with VHs associated with PDR in patients who had not undergone retinopexy. 

In addition to the 2-year results, the investigators wanted to determine the complications with and adherence to intravitreal aflibercept injection monotherapy for PDR-related VH.

The eligible patients were randomly assigned postoperatively to mandatory aflibercept injections either every 8 weeks or every 16 weeks with as-needed injections because of progressive PDR or diabetic macular edema. 

The primary outcome was safety issues that included large losses of vision or proliferative consequences of PDR. The secondary outcomes included VA, anatomic, functional, and treatment outcomes, Marcus said.



Investigators research safety, efficacy of endolaserless vitrectomy.


Ophthalmology Times: October 1, 2020