The phase 1 study of NGM621 (NGM Biopharmaceuticals), a novel, humanized, monoclonal IgG1 antibody, showed promising results that support the continued clinical development of the drug to treat geographic atrophy (GA). 

The drug was well tolerated without development of serious adverse effects, according to Charles C. Wykoff, MD, PhD, of Retina Consultants of Houston, Texas.

Tool offers ultra-rapid cooling for intravitreal injections


“Overactivation of the complement cascade has been implicated repeatedly in GA pathogenesis,” he explained. “C3 represents the central point of convergence for the 3 activation pathways in the eye: the classical, lectin, and alternative pathways.”

NGM621 works by inhibiting C3 cleavage, thereby preventing C3a and C3b subunit generation and inhibiting downstream propagation of the complement cascade. Because of its design, it has a high affinity for C3.



The trial evaluated the safety and tolerability of the single and multiple intravitreal injections of the treatment in patients with GA that was at least 2.5 mm

 and best-corrected visual acuities (BCVAs) ranging from 20/80 to 20/400. 

The secondary outcomes were to determine the pharmacokinetic profile and the immunogenicity of the treatment.

Intravitreal injections and endophthalmitis: Does lidocaine gel change the risk of the infection?

The study included a total of 15 eyes in 4 cohorts. The patients in 3 cohorts of 3 patients each received 1 injection in ascending doses: 2 mg per eye, 7.5 mg per eye, and 15 mg prt eye; the 6 patients in cohort 4 received 2 doses of 15 mg/eye separated by 4 weeks, Wykoff recounted.


Patients were a mean age of 78.6 years, with a mean VA of about 20/250. The mean area of GA was large at 14.9 mm.

The patient demographics were well balanced across the 4 cohorts at baseline. All patients completed the study.

Wykoff noted that no vision-related safety signals or safety/tolerability signals were detected in any cohorts that were attributable to NGM621. No cases of endophthalmitis, intraocular inflammation, or choroidal neovascularization developed during the 12-week follow-up.

Any ocular adverse events were those normally associated with intravitreal injections.

Improve patient comfort with intravitreal injections

The maximal dose of 15 mg per eye administered twice was well tolerated with no safety signals associated with the study drug, no serious adverse events, and no deaths.

Both the BCVA and the GA lesion area remained stable over the 12-week course. The mean IOP 15 minutes after the treatment increased transiently by about 5 mm Hg and returned to the baseline level after 1 hour and remained there through the follow-up.

Wykoff noted that the mean serum pharmacokinetics of the study drug was linear and dose-proportional with low accumulation across the single-dose cohorts and in cohort 4 after every-4-week repeat intravitreal dosing. 

The serum exposure of the study drug was below concentrations that produce systemic complement inhibition at the highest study dose.

Study outlines use of intravitreal injection of allogeneic human retinal progenitor cells to treat RP

Following the 15-mg dose, the drug was predicted to achieve more than 90% C3 target engagement in the eye for 7 weeks after 1 intravitreal dose based on the pharmacokinetics/pharmacodynamics model.

“The modeling supports investigating an every-8-week intravitreal dosing regimen,” he said.

Moreover, NGM621 serum exposure appeared dose-proportional, indicating linear pharmacokinetics in the studied range. The pharmacokinetics/pharmacodynamics model supports dosing intervals up to 8 weeks.

The trial also found that NGM621 was well tolerated up to 15 mg dosed twice, with no safety signals and no serious adverse drug-related events. 

The drug is now in the phase 2 CATALINA study (NCT04465955) of 240 patients randomized to dosing every 4 or 8 weeks compared with sham treatment.


e: ccwmd@retinaconsultantstexas.com
This article was adapted from Wykoff’s presentation at the Bascom Palmer Eye Institute Angiogenesis, Exudation and Degeneration 2021 virtual annual meeting. He is a consultant to and performs research for NGM Biopharmaceuticals.

Articles

Investigation evaluates safety of single and multiple intravitreal injections. 

Phase 1 trial shows NGM621 for GA is well tolerated by study participants

Innovative drug delivery methods are reshaping modern medicine and will inevitably define the future of ophthalmology. 

Strategies that minimize the burden on patients and provide excellent outcomes and safety are increasingly available via novel drug delivery methods.

In ophthalmology, these novel technologies offer sustained drug delivery to targeted tissues, often bypassing the ocular surface and obviating concerns about preservatives found in topical formulations. 

Real-world outcomes validate intraocular drug delivery method



Notable examples of these approaches to ophthalmic drug delivery include dexamethasone intraocular suspension 9% (Dexycu; EyePoint Pharmaceuticals, Inc), dexamethasone ophthalmic insert 0.4 mg (Dextenza; Ocular Therapeutix), and bimatoprost implant 10 μgµ(Durysta; Allergan).



Implementing ways to take treatment out of the hands of patients became even more imperative over the past year as the pandemic and government mandates influenced social behaviors. 

For example, elderly patients who might normally have had assistance from family or friends had to obtain and administer ophthalmic drugs on their own.

Regarding the cataract portion of my practice, both Dexycu and Dextenza play an integral role. They are similar in that they make it possible, in most cases, for patients to avoid conventional steroid drops after surgery. 

Both deliver dexamethasone (in different concentrations) in a sustained-release manner through the first postoperative month. Their distinction, however, primarily lies in the delivery method.

Dexycu, which is formulated using proprietary Verisome sustained-release technology, is a hydrophobic, bioerodible liquid steroid depot that is injected into the posterior chamber at the end of surgery. 

 Study: Dexamethasone intraocular suspension 9% offering high surgeon, patient satisfaction after cataract surgery

Once injected, it forms a 2-mm sphere that delivers a bolus of dexamethasone and tapers over the first few weeks after surgery. 

In the controlled clinical studies that supported Dexycu’s FDA approval, the drug provided a significant anti-inflammatory efficacy that began early and was sustained throughout the postoperative period.

 

These findings reflect what I’ve found in my patients as well. Following the positive experiences reported by other surgeons, I’ve been administering Dexycu directly into the capsular bag, which has been helpful in keeping the drug depot reliably in place.

Although the pivotal trials for Dexycu were conducted in cataract surgery, it is approved for any ocular surgery and has been used for postoperative inflammation control in minimally invasive glaucoma surgeries and even vitreoretinal surgeries.

Dextenza is inserted into the lower lid tear canaliculus at the end of cataract surgery, where it elutes dexamethasone onto the ocular surface, providing an ancillary benefit of punctal occlusion, and gradually resorbs after approximately 30 days.

New options continue to fill drug delivery pipeline


Regarding its potential benefit to the ocular surface, I am also currently conducting a clinical trial evaluating Dextenza in conjunction with the Systane iLux (Alcon) meibomian gland dysfunction treatment device.

Durysta, the most recent entrant into the market, is the first intracameral biodegradable sustained-release implant designed to lower IOP in patients with open-angle glaucoma or ocular hypertension. 

This drug’s FDA approval was based on the results of 2 phase 3 studies in a substantial cohort of patients that compared Durysta with twice-daily topical timolol drops. 

In both studies, Durysta reduced IOP by approximately 30% from baseline over the 12-week primary efficacy period.

I find Durysta’s capabilities very interesting, especially as a cornea specialist who has done considerable research into the interplay between dry eye and glaucoma.

Single administration of intracameral bimatoprost implant: IOP lowering, safety


As positive data accumulate on these drugs, I’ve incorporated them into my practice—as I do with all new technologies that I deem worthwhile—by identifying patients I think will benefit from them. Then I use the products to provide the highest quality of care.

However, as is often the case with novel drugs and devices, some providers are interested in pursuing their use but are held back by concerns about reimbursement. 

It’s important to understand that because these products have been granted transitional pass-through payment status by Centers for Medicare and Medicaid Services (CMS), it is possible to use them to your patients’ advantage without negatively affecting your practice or ambulatory surgical center’s bottom line. In fact, reimbursement is typically average sales price plus 6%.

Although transitional pass-through status has been a part of the CMS reimbursement landscape for more than 20 years, many ophthalmologists are either unfamiliar with it or deterred by its complexity. 

Educating yourself and your administrative staff about the nuances of this process is key to unlocking its rewards.

CMS 2022 Physician Fee Schedule includes payment cut

Pass through is termed “transitional” because it is meant to be a temporary designation afforded newly approved products for a few years as they transition to widespread use. 

When pass-through status is bestowed on a product by CMS, a Healthcare Common Procedure Coding System code is promulgated—first a C-code and then a J-code. 

These codes must be used during billing for the practice to receive reimbursement.

Pass-through status is conferred for at least 2 years but is typically not longer than 3 years. This gives physicians time to learn about these products and their real-world performance. 

Additionally, CMS collects utilization data during this period and employs this information when determining how to adjust the payment rate after transitional pass-through status expires. 

Product utilization during this time is crucial to provide sufficient claims data for CMS to make an accurate determination regarding future reimbursement.

Tear tests in eye care: Use, reimbursement outlined

In essence, transitional pass-through status is intended to encourage the use of newly FDA-approved medical devices, drugs, and biologics across all fields of medicine and to boost Medicare patients’ access to these innovative therapies by temporarily paying more than established facility fees.

During a product’s pass-through status phase, CMS evaluates utilization and claims data to decide whether it is an effective innovation that should have its own reimbursement code once pass through is over. 

If utilization shows that it doesn’t justify its own code, it will end up getting bundled into the facility fee, which will increase slightly but not enough to cover the cost of the product. 


As I see it, the onus is on us as physicians to make use of innovative products that benefit our patients during the pass-through period to help ensure our patients can continue to have access to these products once this phase is complete. 

Programs such as EyePoint Assist can help practices navigate coding, obtain samples, and even provide direct reimbursement in the event of claims denial (see 

Practical tips, pearls to help ease patients' financial burdens

All patients benefit from drug delivery advances, and most are eager not to self-administer eye drops. But the ones who benefit the most tend to be those who have challenges with memory, vision, or dexterity that make it difficult to use eye drops. 

Once again, this confluence of issues has been compounded by the ongoing challenges associated with COVID-19, which in some instances has made it more difficult than usual for patients to access assistance.

Using pass-through products such as Dexycu or Dextenza may involve a few more administrative steps at the moment, but taking postoperative inflammation management out of the hands of the patients is invariably worth the effort. 

In addition to discussing this with the patient and perhaps their caregiver or family member, our surgical coordinators contact the patient’s insurer, if applicable.

Together, we determine if the pass-through drug is covered and how to get precertification approval—a process made easier with resources from the manufacturers of each product. 

In many practices, a substantial proportion of patients will be covered with Medicare Part B, to which pass-through status directly applies; for those under Medicare Advantage or commercial insurance, coverage depends on local or regional contracts, and the support provided by manufacturers can help manage this complexity. 

As with many new processes, increasing familiarity results in streamlining and greater ease within a practice.

Dexycu and Dextenza have been granted pass-through status.

Pass-through payments have no direct effect on physicians’ fees.

CMS, not the drug manufacturers, determines the price of pass-through products.

The budget for pass-through payments is set aside by CMS a year in advance.

Congress created pass-through payments to ensure that new drugs, devices, and biologics are available for patients and are paid for separately from a physician’s bundled payment.

While a product has pass-through status, CMS evaluates utilization and claims data in an effort to decide whether it is an innovation that should eventually have its own reimbursement code.

If you have questions about whether a pass-through product is covered for a particular patient or any other concern regarding reimbursement or usage of these products, contact the manufacturer.

Generally, the companies that have a transitional pass-through product are eager to help practices affordably access these innovative treatments so that patients will get top-tier treatment and utilization rates will support a permanent reimbursement code.

Ensuring pass-through payments are properly processed strengthens our ability to offer patients the latest innovations in drugs and devices. 

Although it may mean navigating an unfamiliar billing process at the start, this effort is critical because it can make a world of difference to our most vulnerable patients who will benefit from advanced drug delivery methods.


Nijm is the founder and medical director of Warrenville EyeCare and LASIK in Warrenville, Illinois; assistant clinical professor of ophthalmology at the University of Illinois Eye and Ear Infirmary in Chicago; and the founder of MDNegotiation.com. She is a consultant for Allergan, EyePoint, and Ocular Therapeutix.

1. Donnenfeld E, Holland E. Dexamethasone intracameral drug-delivery suspension for inflammation associated with cataract surgery: a randomized, placebo-controlled, phase III trial. 

. 2018;125(6):799-806. doi:10.1016/j.ophtha.2017.12.029

2. Donnenfeld ED, Solomon KD, Matossian C. Safety of IBI-10090 for inflammation associated with cataract surgery: phase 3 multicenter study. 

. 2018;44(10):1236-1246. doi:10.1016/j.jcrs.2018.07.015

3. Osher RH, Weinstock RJ. Dexamethasone intraocular suspension 9% in the capsular bag. 

4. Tan NE, Radcliffe N. Outcomes of dexamethasone intraocular suspension during cataract surgery and concomitant cataract-micro-invasive glaucoma surgery (MIGS). 

5. Kiernan DF. Dexamethasone intracameral drug-delivery suspension for inflammation associated with vitreoretinal surgery. 

 2020;5(1):e000491. doi:10.1136/bmjophth-2020-000491

6. Tyson SL, Bafna S, Gira JP, et al. Multicenter randomized phase 3 study of a sustained-release intracanalicular dexamethasone insert for treatment of ocular inflammation and pain after cataract surgery. 

. 2019;45(2):204-212. doi:10.1016/j.jcrs.2018.09.023

7. Shirley M. Bimatoprost implant: first approval. 

. 2020 2020;37(6):457-462. doi:10.1007/s40266-020-00769

8. Nijm LM, De Benito-Llopis L, Rossi GC, Vajaranant TS, Coroneo MT. Understanding the dual dilemma of dry eye and glaucoma: an international review. 

. 2020;9(6):481-490. doi:10.1097/APO.0000000000000327

Understanding nuances of reimbursement for novel, sustained-release ophthalmic drugs can help maximize the opportunity for patients and practice.

Novel ophthalmic pharmaceuticals drive innovation, improve outcomes

Reviewed by Augustine Bannerman and Filippos Vingopoulos, MD

A quick test with active learning algorithms may give physicians a novel way to measure contrast sensitivity (CS) when evaluating patients before 

, according to Augustine Bannerman, an undergraduate research assistant, and Filippos Vingopoulos, MD, both from the Harvard Retinal Imaging Laboratory at Massachusetts Eye and Ear in Boston.

“Contrast sensitivity function [CSF] testing may be a valuable addition to the standard cataract evaluation to enhance surgical decision-making, particularly in patients with subjective visual complaints despite good visual acuity [VA],” Bannerman said.

According to Bannerman, surgical decision-making in the lead-up to cataract surgery is based on subjective visual impairment and not on objective clinically measured visual function outcomes.

Timing and earlier neurolept anesthesia for laser-assisted cataract surgery

In light of this, Bannerman and his colleagues embraced past research on the strong correlation between CS and subjective visual impairment and vision-related daily activities, then went a step further to bypass the current imperfections that limit the CS testing used clinically.


Investigators included 167 eyes, of which 58 eyes were cataractous, 77 were controls, and 32 were pseudophakic, in a study to characterize CSF in patients with cataract and those that were pseudophakic using a novel CSF test with active learning algorithms. 

Participants’ vision was assessed using the Manifold Contrast Vision Meter (Adaptive Sensory Technology). 

Visually relevant cataract was defined as 2+ nuclear sclerosis and a VA of more than 20/50, pseudophakic patients had posterior segment intraocular lenses, and controls had no more than 1+ nuclear sclerosis and no visual complaints.

The primary outcomes were the area under the log CSF (AULCSF), contrast acuity (CA), and CS thresholds at 1, 1.5, 3, 6, 12, and 18 cycles/degree (cpd).

What patients need to know about cataract surgery


The so-called quick CSF test uses "a Bayesian active learning algorithm that maximizes information extraction over a very large set of possible combinations of contrast and spatial frequency that ultimately creates a curve separating visible from invisible stimuli with great test-related repeatability and testing times of 2 to 5 minutes per eye,” Bannerman said.

The investigators reported that the presence of cataract was associated with significantly decreased AULCSF (

 = .04) and contrast threshold at 6 cpd (

An interesting finding, according to Bannerman, was that even in a subgroup of cataractous eyes with very good VA (≥ 20/25), the contrast threshold at 6 cpd was still decreased significantly (

The 6-cpd spatial frequency seems important, he said: The lower or higher spatial frequencies were not affected by cataract. 

These contrast sensitivity deficits detected with the quick CSF test would have been missed with the traditional Pelli-Robson contrast testing, he added.

Cataract surgeons on OR waste: Less is often more

Pseudophakic eyes did not have significantly different contrast outcomes measures compared with the controls.

The quick CSF test detected disproportionate significant contrast deficits at 6 cpd in the various metrics evaluated in cataractous eyes and even in those with good VA, the authors noted.

“CSF testing may be a valuable addition to standard cataract evaluation to enhance surgical decision-making especially in patients with subjective visual complaints despite good VA,” they said.

A potential area of study might be to perform the quick CSF test in pseudophakic eyes with different types of intraocular lenses, the authors said. 

An ongoing study will demonstrate the improved CSF after 

This article is adapted from Bannerman’s presentation at the Association for Research in Vision and Ophthalmology 2021 virtual annual meeting. Bannerman has no financial interest in this subject matter.

Advances help gain clearer image, enhancing decision-making process.

Physicians measure contrast sensitivity in patients with cataract

Worldwide, there are 1.8 billion presbyopes, many of whom have inadequate vision correction.

The large US millennial population, estimated to be 72 million individuals, begins turning 40 this year, adding millions more presbyopes to the mix over the next 15 years.

It is important that we recognize the impact presbyopia has on patients’ lives. 

As ophthalmologists, we know this ubiquitous condition doesn’t threaten ocular health, so it is easy to be dismissive. 

Our patients find it tremendously frustrating. In a recent market research study in which 1000 presbyopic adults ages 40 to 80 were surveyed, 60% ranked the loss of near vision as one of the age-related ailments that has the greatest impact on quality of life—ahead of hearing loss, arthritis, dry eye, and other conditions.

For emmetropes, presbyopia can be particularly incapacitating, because they have never experienced vision problems. 

Suddenly, their ability to use a computer, read price tags, present on a Zoom call, and even enjoy dining out is negatively affected. 

The most common solution, OTC reading glasses, always seems to be in another room or left in the car when needed. My presbyopic patients tell me that reading glasses feel like a scarlet letter, announcing their age to the world.

Even under ideal circumstances, progressive glasses with the reading segment at the bottom of the prescription lens force patients to bob their heads or tuck their chins to bring the object they are viewing into the clear zone. 

Wearing readers (or bifocals or progressives, for that matter) also increases the risk of falls.

This is particularly the case in later presbyopia, when the higher add power can blur steps or curbs on a downward gaze. Additionally, spectacle multifocality impairs edge-contrast sensitivity and depth perception.

It is very good news that eye drops intended to treat presbyopia are being developed and expected to begin entering the US market as early as this year (

As we consider how these drops might affect patients and practices in the future, this is a good time to evaluate what patients need and expect from a topical solution to presbyopia.


In the market research survey, there were high levels of interest in presbyopia-correcting drops across all age groups, genders, and income levels. 

I see this in my own patients. When I mention that drops might be an option for them in the future, their eyes light up immediately.

When asked about the most important features of a presbyopia drop, 96% of the survey respondents cited long duration. Essentially, they wanted it to last as long as possible throughout the day. 

We know patients do not like instilling drops midday for dry eye or glaucoma, and this will likely be no different. Patients do not want to have to have to plan to bring drops with them and then stop what they are doing to instill them. 

When asked more specifically about how long they want the drops to work, 73% of survey respondents said they prefer a duration of at least 7 hours (


Also of great importance to the survey respondents was that the drops work as well as their glasses or contacts, with 94% ranking this highly. 

A large majority of respondents (83%) also felt it is important for adverse effects to be mild or infrequent.

As someone passionate about ocular surface care, I believe a major consideration in prescribing will be the presence of preservatives in these presbyopia-correcting drops that can negatively impact the ocular surface. 

There is significant overlap between presbyopia and dry eye, because both increase in prevalence with age. 

Preservatives like benzalkonium chloride (BAK) interfere with the health of the epithelial microvilli, disrupting tear film homeostasis and exacerbating preexisting ocular surface issues. 

Given that we know patients want presbyopia drops to last all day, I believe a longer-duration drop will have a better safety profile because patients would use it just once a day, rather than increasing their BAK or other preservative exposure with multiple doses per day. Preservative-free options will be ideal.



Emmetropes will be the first group of people to whom I will offer presbyopia-correcting drops because they have never worn glasses and do not perceive glasses as part of their persona. 

About half of people in the key demographic segment for presbyopia-correcting drops (ages 40 to 59) are emmetropes.

I would include post-LASIK emmetropes in this initial group. They have already made a significant investment in their eyes specifically to avoid wearing spectacles.

The second group I would offer drops to would be low to moderate hyperopes. 

These patients are already wearing glasses and sometimes struggle with overmagnification from a near add, so reducing their dependency on glasses will be a big benefit. 

By contrast, low myopes in the –1.50 to –3.00 range likely will be the least interested in presbyopia-correcting drops because they can just remove their glasses for near vision.

The third major group I see benefitting from presbyopia-correcting drops are pseudophakes who had surgery before all the advanced multifocal and EDOF IOLs became available or who opted for monofocal IOLs and still need reading glasses.

Pseudophakes were more likely than phakic patients in the survey to express interest in presbyopia-correcting drops, with 79% of pseudophakes and 91% of premium IOL patients saying they would definitely try the drops if their doctor recommended them, compared with 58% of the entire survey population. 

We also have many pseudophakes who have blended monovision, with one eye targeted for distance and one for intermediate—and neither eye seeing well at near. 

It is hard to say at this stage whether monovision patients will benefit from bilateral or unilateral use of the drops, especially because not all drops that enter the market will have been tested in this subgroup.


There will be much for patients and doctors to learn as presbyopia drops become available and we all gain real-world experience with them. 

I believe we will eventually be able to match drop characteristics to our patients’ needs, just as we currently select presbyopia-correcting IOLs based on patients’ ocular health, vision, and lifestyle. 

The big difference, of course, is that a drop is not a once-in-a-lifetime choice. 

Patients can try different drops and dosing schedules to find the one that provides the best results with the fewest adverse effects for them.

Matossian is founder and medical director of Matossian Eye Associates, an integrated ophthalmology and optometry group practice with 3 offices in Pennsylvania and New Jersey. Matossian Eye is an affiliate of Prism Vision Group. She also serves as a clinical instructor in the Department of Ophthalmology at Temple University School of Medicine. She is a consultant to Allergan and Visus Therapeutics. 

1. Fricke TR, Tahhan N, Resnikoff S, et al. Global prevalence of presbyopia and vision impairment from uncorrected presbyopia: systematic review, meta-analysis, and modelling. 

. 2018;125(10):1492-1499. doi:10.1016/j.ophtha.2018.04.013

2. National population by characteristics: 2010-2019. United States Census Bureau. Updated June 17, 2020. Accessed January 15, 2021. www.census.gov/data/datasets/time-series/demo/popest/2010s-national-detail.html

3. Donnenfeld ED. Clinical considerations for topical presbyopia drop therapies. Burke Healthcare Research. Presented at: 2020 International Society of Presbyopia (ISOP) conference. November 11, 2020.

4. Lord SR, Dayhew J, Howland A. Multifocal glasses impair edge-contrast sensitivity and depth perception and increase the risk of falls in older people. 

. 2002;50(11):1760-1766. doi:10.1046/j.1532-5415.2002.50502.x

5. Vitale S, Ellwein L, Cotch MF, Ferris FL 3rd, Sperduto R. Prevalence of refractive error in the United States, 1999-2004. 

. 2008;126(8):1111-1119. doi:10.1001/archopht.126.8.1111

Patients can try different drops and dosing schedules to improve outcomes.

Expectations are on rise for presbyopia-correcting therapeutic

® Research Scholar Honoree Program is dedicated to the education of retina fellows and residents by providing a unique opportunity for fellows and residents to share notable research and challenging cases with their peers and mentors. The program is supported by an unrestricted grant from Regeneron Pharmaceuticals.





The use of intravitreal anti-VEGF injections are the standard of care for the treatment of common retinal diseases. These include neovascular age-related macular degeneration (AMD), retinal vein occlusion, and diabetic macular edema.

Although anti-VEGF medications have excellent safety profiles, acute bacterial endophthalmitis remains an uncommon but potentially devastating complication. Multiple studies have evaluated procedure-related risk factors associated with postinjection endophthalmitis. 

Patients taking immunosuppressive medications have an increased risk for endogenous endophthalmitis.


To evaluate the effect of systemic immunosuppression on the rates and outcomes of endophthalmitis after intravitreal anti-VEGF injections.


A retrospective, single-center, comparative cohort study.


All eyes receiving intravitreal anti-VEGF (bevacizumab, ranibizumab, and aflibercept) injections from January 1, 2016 to September 1, 2019 were included in this study. 

The trial investigators used billing records and endophthalmitis logs to identify patients who developed endophthalmitis following the injections. 

They reviewed the charts of all patients who were treated for endophthalmitis, and confirmed the diagnosis.

Endophthalmitis was defined as patients who presented with a clinical suspicion that was high enough to warrant either intravitreal antibiotic injection with vitreous/aqueous tap or pars plana vitrectomy with injection of antibiotics.

The investigators divided the cases into an “immunosuppression” group and a “no immunosuppression” group. 

They defined the immunosuppression group as any patient taking systemic medication from the following classes at the time of intravitreal injection: corticosteroids, alkylating agents, antimetabolites, calcineurin inhibitors, mammalian target of rapamycin (mTOR) inhibitors, biologics, monoclonal antibodies, and chemotherapeutic medications.

The primary outcome measure was the rate of endophthalmitis in the immunosuppression group and no immunosuppression group. 

Secondary outcome measures included visual acuity (VA) outcomes and microbiologic flora in both groups.


Of 269,047 intravitreal injections administered over the study period, 1300 (0.48%) patients were taking a systemic immunosuppressive medication at the time of the causative injection. 

Five of 1300 (0.38%; 1 in 260 injections) cases of endophthalmitis occurred in the immunosuppression group, and 100 of 269,047 (0.037%; 1 in 2690 injections) cases occurred in the no immunosuppression group (odds ratio, 9.86; 95% CI, 4.0-24.2; 

Of the 5 cases of presumed endophthalmitis in the immunosuppression group, 4 patients were taking oral prednisone and 1 patient was taking mycophenolate mofetil at the causative injection. 

Three of 5 (60%) eyes in the immunosuppression group were culture positive compared with 32 of 74 (43%) cases in the no immunosuppression group (

Patients with presumed endophthalmitis presented a mean (SD) 2.8 (1.9) days after injection in the immunosuppression group compared with 5.3 (5.4) days in the no immunosuppression group (difference, 2.51 days; 95% CI, 0.15-4.87; 

 = .040).

Mean (SD) logMAR (Snellen equivalent) VA at endophthalmitis presentation was 2.11 (1.2; approximately 20/2500) in the immunosuppression group vs 1.8 (0.91; approximately 20/1260) in the no immunosuppression group (

 = .465). 

At 6 months after endophthalmitis treatment, mean (SD) logMAR VA was 1.22 (1.3; approximately 20/330) for the immunosuppression group compared with 0.96 (0.93; approximately 20/180) for the no immunosuppression group (adjusted difference, 0.253; 95% CI, –0.99 to 0.48), 


Patients taking systemic immunosuppressive medications undergoing intravitreal injections may be at increased risk of postinjection endophthalmitis and may have earlier symptom onset. 

However, visual outcomes were similar between the 2 groups 6 months after endophthalmitis treatment.


Patel is affiliated with Wills Eye Hospital, Mid Atlantic Retina and Thomas Jefferson University in Philadelphia, Pennsylvania. He has no financial disclosures related to this topic.

Systemic immunosuppression may prevent devastating complication in patients.

Focusing on postinjection endophthalmitis 

The interim data from the FOCUS trial (NCT03846193), a first-in-human phase 1/2 gene therapy study, showed that GT005 (Gyroscope Therapeutics Limited), an investigational gene therapy, is well tolerated in patients with geographic atrophy (GA) secondary to 

GT005 is designed to induce local production of recombinant complement factor I (CFI).

Study: Gene therapy could preserve vision in patients with retinal disease, serious retinal injury

GT005 designed to induce local production of recombinant complement factor I.

Ophthalmology Times: July 15, 2021

Phase 1 trial shows NGM621 for GA is well tolerated by study participants

Novel ophthalmic pharmaceuticals drive innovation, improve outcomes

Physicians measure contrast sensitivity in patients with cataract

Expectations are on rise for presbyopia-correcting therapeutic

Focusing on postinjection endophthalmitis

Addressing GA by downregulating overactive complement system

The benefits of cryopreserved amniotic membrane during COVID-19

Choroidal hypertransmission defects on en face OCT imaging predict geographic atrophy in patients

CRISPR technology: A hot topic in gene therapy

VA and visual function go the way of ocular inflammation

Bariatric surgery may lead to decreased risk of cataract

AAVCOVID vaccine: A combination of factors harnessing COVID-19

Pivotal study data drive glaucoma patient treatment decisions

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