Investigators from McGill University, Quebec, Canada, and Stanford University, Palo Alto, CA, reported that young smokers had more ocular symptoms resulting from cigarette smoking than those who smoked electronic cigarettes. However, those who used both reported severe to very severe ophthalmic symptoms, according to Anne Xuan-Lan Nguyen, from McGill University, Quebec, Canada, first author of the study.

The investigators conducted an observational, cross-sectional online survey to determine the frequency and severity of ocular symptoms in young e-cigarette and cigarette users.

A total of 4,351 Americans aged 13 to 24 years responded to the survey questions regarding the use or non-use of nicotine e-cigarettes and cigarettes and the use during the previous 7 and30 days.

Dual users were defined as those who used both products. The outcomes included the general vision status and frequency and severity of ocular symptoms that included ocular discomfort, pain, burning, itching, redness, dryness, glare, blurry vision, eye strain, and headaches.

Ms. Nguyen reported that42.5% to 70.7% of all respondents reported no ocular symptoms.

Among dual uses, 1.1% to 3.9% reported severe to very severe symptoms; 0.9% to 4.3% of dual users reported frequent symptoms occurring daily. Both of these rates were significantly higher than among the respondents who used only e-cigarettes or only cigarettes (

 < 0.05). Those who used cigarettes alone reported more severe and frequent symptoms than those who used e-cigarettes alone (

The investigators pointed out that this large, population-based study offers new perspectives on ocular symptoms in young users of e-cigarettes and cigarettes.

“More severe and frequent ocular symptoms occurred in young Americans using both cigarettes and e-cigarettes. Dual users should cease and reduce their use of such products to prevent and minimize ocular risks,” the authors concluded.

They also recommended that health care providers document the use of smoking products in their patients, which may result in better prevention and counseling in the ophthalmic patient population.

Articles

Those who used both traditional and electronic cigarettes reported severe to very severe ophthalmic symptoms.

Fewer ocular symptoms linked to e-cigarettes than traditional cigarettes

The 2-year results of the TENAYA and LUCERNE studies indicated that faricimab (Vabysmo, Genentech), the first intraocular bispecific antibody that inhibits both angiopoietin-2 and vascular endothelial growth factor-A was safe and efficacious for treating neovascular age-related macular degeneration (AMD).

Rishi Singh, MD, FASRS, reported the highlights of the pooled results of the trials on behalf of the study investigators.

TENAYA and LUCERNE were Phase 3 global, randomized, double-masked 112-week trials designed to assess the efficacy, safety, and durability of faricimab in treatment-naïve patients with neovascular AMD.

At week 60, patients in the faricimab arm were treated according to a protocol-driven treat-and-extend–based regimen.

Singh reported that, compared with baseline, gains in vision and decreased central subfield thicknesses following treatment with faricimab out to every-16-week dosing were similar to those achieved with aflibercept (Eylea, Regeneron) with every-8-week dosing with fewer injections, through week 112.

At week 112, more than 60% of patients treated with faricimab achieved every-16-week dosing and about 80% achieved every-12-week dosing or better.

Those who needed treatment every 8 weeks generally had worse baseline ocular characteristics versus extended treatment intervals, he pointed out.

“Early and rapid treatment interval extension with faricimab was associated with stable visual gains and anatomic outcomes through week 112,” Singh commented. 

In support of this, the analysis showed that most patients on every-12-week dosing at week 60 achieved every-16-week-dosing at week 112.

Every-8-week dosing was associated with tight anatomic control, and most of these patients on every-8-week dosing at week 60 were on extended dosing intervals at week 112.

Faricimab was well-tolerated with an acceptable safety profile through week 112.

The AVONELLE-X long-term extension study will continue to evaluate the efficacy, durability, and safety of faricimab in patients with neovascular AMD.

Faricimab for nAMD: Safe, effective, lower treatment burden compared with aflibercept in pooled TENAYA, LUCERNE Phase 3 trials

On Friday, the Janssen Pharmaceutical Companies of Johnson & Johnson announced the primary results from the Phase 1/2 study evaluating the investigational gene therapy botaretigene sparoparvovec (formerly AAV-RPGR) in patients with the inherited retinal disease X-linked retinitis pigmentosa (XLRP) associated with the retinitis pigmentosa GTPase regulator (RPGR) gene.

The announcement was made on Friday during the late-breaking oral presentations at the Retina Subspecialty Day at the American Academy of Ophthalmology’s 2022 annual meeting at McCormick Place in Chicago.

According to the company, treatment with botaretigene sparoparvovec was found to have an acceptable safety profile, and efficacy assessments in this proof-of-concept study demonstrated encouraging improvements in retinal sensitivity, visual function and functional vision.

Janssen pointed out in a news release that these findings and additional updates, including data from a Phase 1 trial of investigational gene therapy JNJ-81201887 (JNJ-1887) for patients with geographic atrophy (GA), a late-stage and severe form of age-related macular degeneration (AMD).

XLRP is a rare condition estimated to impact one in 40,000 people globally.

 People with XLRP have progressive vision loss, starting in childhood with night blindness.

 Over time, they lose their peripheral vision leading to legal blindness by middle age.

 Botaretigene sparoparvovec is being investigated in collaboration with MeiraGTx Holdings plc to treat patients with XLRP caused by disease-causing variants in the eye-specific form of the RPGR (RPGR ORF15) gene.

The company also noted that through a one-time administration, botaretigene sparoparvovec is designed to deliver functional copies of the RPGR gene to counteract the loss of retinal cells with the goal of preserving and potentially restoring vision for those living with XLRP. Currently, there are no approved treatments for XLRP.

"Individuals living with XLRP often begin to experience symptoms in childhood, and as retinal degeneration progresses toward blindness, they can start to feel a sense of hopelessness as there are no treatments to turn to," said Michel Michaelides, BS., MB, BS, MD (Res), FRCOphth, FACS, a consultant ophthalmologist, Moorfields Eye Hospital, Professor of Ophthalmology, University College London and lead investigator. "These results from the MGT009 study are promising, as they represent the potential for botaretigene sparoparvovec to preserve vision and ultimately restore hope for these patients."

Moreover, the company noted that the primary endpoint of the MGT009 study (

) was safety, with secondary endpoints measuring changes in assessments of three domains of vision—retinal sensitivity, visual function and functional vision—at specified time points post-treatment.

 In the study's dose escalation and expansion phases, significant sustained or increased functional improvement in each visual domain was observed in participants treated with botaretigene sparoparvovec compared to the randomized untreated control arm of the study at six months post-treatment.

According to Janssen, analyses of the pooled low and intermediate dose cohorts demonstrated improvement in retinal sensitivity in the treated eyes compared to untreated eyes in the randomized concurrent control arm as measured by both full-field static perimetry and microperimetry.

 An improvement in mean retinal sensitivity as measured by static perimetry in the central 10-degree area of the retina was observed at six months in the treated eyes compared to untreated eyes in the randomized concurrent control arm [in the full analysis of pooled low and intermediate doses across adults: 1.96 decibel (dB); (±95% CI: 0.59, 3.34); and in the sensitivity analysis when applying the Phase 3 criteria: 2.42 (0.91, 3.93)].

The company also noted that as part of the study, patients performed a functional vision assessment using a 

 to assess their ability to navigate through simulated real-life obstacles across a broad range of controlled light. At week 26, improvement in walk time was observed between the treated eyes in the low and intermediate dose cohorts and the untreated eyes in the randomized concurrent control arm at low illumination levels (full analysis nominal p-value < 0.05 at lux 1 and lux 16; in the sensitivity analysis when applying the Phase 3 criteria nominal p-value < 0.01 at lux 1, lux 4 and lux 16).

The safety profile of botaretigene sparoparvovec observed in MGT009 was consistent with previous reports.

 Botaretigene sparoparvovec demonstrated an adverse event (AE) profile that was anticipated and manageable.

 Most AEs were related to the surgical delivery procedure, were transient and resolved without intervention.

 A total of three serious adverse events (SAEs) were observed in the overall Phase 1/2 MGT009 clinical study; two SAEs, which were previously reported, were observed in the dose-escalation phase of the study (n = 10; one retinal detachment and one panuveitis in the low dose cohort), and a single additional SAE of increased intraocular pressure was observed in the dose escalation phase and resolved with treatment.

"Without an approved treatment option available, people with XLRP are faced with the inevitable fate of going blind in the prime of life," said James List, MD, PhD, Global Therapeutic Area Head, Cardiovascular, Metabolism, Retina & Pulmonary Hypertension, Janssen Research & Development, LLC. "We're in a race to save sight for these patients and are encouraged by the strength of the data that we've shared so far. We look forward to advancing the clinical development of botaretigene sparoparvovec as part of our mission to preserve and potentially restore vision for these patients."

Further sensitivity analysis was conducted on study participants by applying the Phase 3 LUMEOS (

) study eligibility criteria that corroborated the endpoints selected for the Phase 3 study.

 Currently, the LUMEOS study of botaretigene sparoparvovec for the treatment of patients with XLRP with disease-causing variants in the RPGR gene is actively dosing patients.

Phase 1 data evaluating JNJ-1887 in geographic atrophy

Janssen also presented late-breaking data from a Phase 1, open-label, multicenter, dose-escalation, safety and tolerability study (

) of a single intravitreal injection of JNJ-1887 in patients with advanced non-exudative (dry) age-related macular degeneration (AMD) with GA. GA is an irreversible condition that affects more than five million individuals worldwide.

 It has a devastating impact on GA patients' health-related quality of life, including their ability to read, drive and perform other day-to-day activities.

 In this study, patients (n = 17) were sequentially enrolled at a low, intermediate and high dose without steroid prophylaxis, and all three doses of JNJ-1887 met the primary endpoint of safety over the two-year follow-up period.

 In addition, the supportive efficacy measures, including evaluation of GA lesion growth rates, showed a continual decline in lesion growth over six-month increments.

 These results are the first shared from the Company's common eye disease portfolio and indicate further evaluation of this investigational gene therapy is warranted.

About the Phase 1/2 MGT009 trial and botaretigene sparoparvovec

) was an open-label, multicenter dose escalation study that enrolled patients aged five years and older with X-linked retinitis pigmentosa (XLRP) caused by disease causing variants in the retinitis pigmentosa GTPase regulator (RPGR) gene at multiple sites in the United States and the United Kingdom. The primary endpoint was safety and tolerability; secondary endpoints assessed retinal sensitivity, visual function and functional vision.

The clinical study was composed of three parts: dose-escalation, pediatric dose-confirmation and an expansion phase. In the dose escalation phase, adult patients were treated at three escalating doses of botaretigene sparoparvovec; a low (2x1011 vg/mL), an intermediate (4x1011 vg/mL), and a high (8x1011 vg/mL) dose. In the expansion phase, 42 adult male patients were randomized to either immediate treatment with one of two low or intermediate doses or an untreated concurrent control arm with deferred treatment. At six months, the untreated control arm was randomized to receive either the low or intermediate treatment doses. Botaretigene sparoparvovec was administered through subretinal delivery in only one eye. The adult patients received treatment at three doses. The pediatric cohort (n = 3) was only treated with an intermediate dose of botaretigene sparoparvovec.

Botaretigene sparoparvovec has been granted Fast Track and Orphan Drug designations by the U.S. Food and Drug Administration (FDA) and PRIority MEdicines (PRIME), Advanced Therapy Medicinal Product (ATMP) and Orphan designations by the European Medicines Agency (EMA).

About the Janssen and MeiraGTx strategic collaboration

In January 2019, Janssen Research and Development, LLC entered into 

a worldwide collaboration and license agreement 

with MeiraGTx Holdings plc, a clinical-stage gene therapy company, to develop, manufacture and commercialize its clinical-stage inherited retinal disease portfolio. Botaretigene sparoparvovec is being developed as part of a collaboration and license agreement. In addition to forming a research collaboration to explore new targets for other inherited retinal diseases, Janssen is working with MeiraGTx to build core capabilities in viral vector design, optimization and manufacturing.

About the Phase 1 JNJ-1887 trial and JNJ-1887

JNJ-81201887 (JNJ-1887), formerly referred to as AAVCAGsCD59, is an investigational gene therapy for the treatment of people with geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD). JNJ-1887 is designed to increase the expression of a soluble form of CD59 (sCD59) intended to protect retinal cells to slow and prevent disease progression. JNJ-1887 was evaluated in a Phase 1 clinical trial (

), an open-label, single-center dose escalation study to determine the safety of JNJ-1887 in adults 50 or older with advanced dry AMD with GA. The patients were treated at three escalating doses of JNJ-1887 without steroid prophylaxis through a single intravitreal injection in one eye.

This Phase 1 study met its primary endpoint of safety in all doses of JNJ-1887 (n = 17), with supportive efficacy measures including evaluation of GA lesion growth rates, which showed a continual decline in lesion growth over six-month increments.

JNJ-1887 has been granted Fast Track designation by the FDA and Advanced Therapy Medicinal Product (ATMP) designation by the European Medicines Agency (EMA).

1. Michaelides, M et al. Ph1/2 AAV5-RPGR (Botaretigene Sparoparvovec) Gene Therapy Trial in RPGR-associated X-linked Retinitis Pigmentosa (XLRP). Abstract #30071754. Presented at the 2022 American Academy of Ophthalmology Annual Meeting.
2. Boughman JA, Conneally PM, Nance WE. Population genetic studies of retinitis pigmentosa. 

. 1980;32(2):223–235.
3. Fishman GA. Retinitis pigmentosa. Genetic percentages. 

. 1978;96(5):822–826. doi:10.1001/archopht.1978.03910050428005.
4. Wang DY, Chan WM, Tam PO, et al. Gene mutations in retinitis pigmentosa and their clinical implications. 

. 2005;351(1-2):5-16.
5. Cohen, MN et al. Phase 1 Study of JNJ-81201887 Gene Therapy in Geographic Atrophy (GA) Due to Age-related Macular Degeneration (AMD). Abstract #30071749. Presented at the 2022 American Academy of Ophthalmology Annual Meeting.
6. Singh RP, Patel SS, Neilsen JS, et al. Patient-, caregiver- and eye care professional-reported burden of geographic atrophy secondary to age-related macular degeneration. 

Janssen noted that results from Phase 1/2 MGT009 study demonstrate safety profile of investigational gene therapy botaretigene sparoparvovec (AAV-RPGR) and suggest sustained vision improvement in patients with X-linked retinitis pigmentosa.

Late-breaking: Janssen announces data from 2 gene therapy programs

Ines Lains, MD, PhD, and colleagues from the Massachusetts Eye and Ear, Harvard Medical School, Boston, reported that adjunct treatment with intravitreal antivirals or early pars plana vitrectomy (PPV) did not improve the rates of retinal detachment (RD) in patients with acute retinal necrosis (ARN).

ARN is rare but can have devastating visual consequences, Lains explained. Over time, patients with ARN have a high risk of developing retinal traction and necrotic retinal breaks, which can lead to the development of a RD.

“RD is one of the most common consequences of ARN,” she said. Systemic antivirals are the mainstay treatment for ARN, and even though clinicians may empirically add intravitreal antivirals or early PPV, data on this topic remains controversial.

The investigators conducted a cross-sectional retrospective cohort study using IRIS Registry data to determine the association between the initial treatment regimen for ARN and RD rates at 6 and 12 months.

The researchers identified 533 eyes of 457 patients that met their criteria. Among them, 358 cases (67.2%) received only systemic antivirals, while 155 (29.1%) received adjunctive intravitreal antivirals, and 20 (3.8%) underwent early PPV.

“At 6 months, the rates of RD were comparable among eyes treated with systemic antivirals alone (19.6%), adjunctive intravitreal antivirals (18.7%, 

 = 0.51),” they reported. Similar results also were seen at the 12-month evaluation (

The results also showed that, compared to use of systemic antivirals alone, treatment with adjunctive intravitreal injections or early PPV did not affect the time to development of RDs (

Lains commented, “To our knowledge, this is the largest dataset of patients with ARN that has been analyzed to date. Our results suggest that adjunctive treatment with intravitreal antivirals or early PPV do not improve rates of RD rates in patients with ARN. These findings are important because they support that, despite the theoretical advantages of these adjunctive strategies, systemic antivirals - the current mainstay of ARN treatment - are appropriate and provide similar outcomes, thus contributing to guide management of this blinding disease.”

The results also showed that, compared to use of systemic antivirals alone, treatment with adjunctive intravitreal injections or early pars plana vitrectomy did not affect the time to development of retinal detachments.

Acute retinal necrosis: Retinal detachment rates are unaffected by early treatment with intravitreal antivirals, vitrectomy 

This transcript has been lightly edited for clarity.

 We're joined today with Dr. Justis Ehlers, who is presenting this year at the American Academy of Ophthalmology. Welcome. Dr. Ehlers, could you tell us a little bit more about your talk this year?

 Sure, Sheryl. Thank you so much for having me; it's a pleasure to be able to share a little bit about the data that we're presenting at the Academy meeting.

The focus of the talk, and as some of the research that we're presenting is really around the importance of understanding what's going on from a fluid dynamics standpoint in wet macular degeneration, and how that may impact visual outcomes. There's been a lot of research that suggests that the presence of different fluids may have different impacts on overall visual acuity. In particular, some of the early data has said that subretinal fluid may be associated with better visual acuity and intraretinal fluid may be associated with more significant visual acuity loss.

Interestingly, in some of these studies, they've actually demonstrated that the presence of subretinal fluid may actually be better than not having any fluid in terms of vision. And we wanted to dive into that a little bit more in terms of evaluating ways to look at the OCT, that may have a better understanding for us as clinicians.

And what we were able to do is, using some advanced image processing, is look at the overall intact aspect of the ellipsoid zone and the integrity that's there. And really judging whether or not there may be underlying atrophy.

And what we found was interesting, and that was was that if the outer retina was intact, the retina being dry was clearly the best visual acuity outcome, really suggesting that that really is what we should push for, as clinicians. Subretinal fluid being present was the second in terms of overall visual acuity outcomes, and then intraretinal fluid, and then actually underlying atrophy being the overall worst visual acuity outcomes.

And so you can see how understanding that key feature of the outer retina really drives the difference that may push outcomes towards more limited visual acuity when you sum the entire population together.

The last piece that we looked at was this concept around volatility. And that is, is that if the fluid is changing significantly, does that have an impact overall? And one of the things that we did find that I think was sort of unexpected, was that dynamic subretinal fluid, so that is that fluid that's changing from visit to visit, appears to have a more deleterious effect on visual acuity than fluid that's static.

And so again, really understanding and as we have more and more therapeutics available to us to understand what's happening on a really monthly, and really weekly basis, for these patients will be helpful to understand how we can optimize their outcomes overall.

 Excellent. And what would be the take-home message for the clinician in their daily practice?

 I think you'll one of the key take-home messages is just use caution in terms of how quickly you extend patients, and really understanding early on--is fluid resolving? And you're not just capturing that. And I think you know, striving for the best fluid outcome early on in treatment, in terms of resolution are really the things that I've taken away from this.

 Well, thank you so much for sharing that. We look forward to learning more about your presentation.

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At AAO 2022, Justis Ehlers, MD, presented a talk entitled, "Defining the Fluid Problem in Neovascular AMD: To Dry or Not to Dry?"

Understanding fluid dynamics in wet macular degeneration

A study of dry eye disease (DED) in children found that the average age of onset of DED is at 12.51 years compared with the average of 61.06 years in adults. The highest prevalence in children was seen between 12 to 15 years of age, according to lead author Vivian Paraskevi Douglas, MD, DVM, MBA, MSc, and colleagues from Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston.

Although DED is highly prevalent in adults, with rates ranging from 5% to 50%, little is known about the disorder in pediatric patients, which sparked the interest in this study.

The investigators used the extensive data in the American Academy of Ophthalmology IRIS® (Intelligent Research in Sight) Registry to study the difference between the pediatric and adult populations.

Almost 5 million patients in the IRIS Registry had received at least one diagnosis of DED between 2013 and 2019; of those, 203,171 were children under 18 years of age and 4,592,808 were adults.

Douglas and associates collected data on biologic sex, race, ethnicity, and US geographic region of residence.

The data breakdown showed that DED was diagnosed in females significantly more often compared with males. More cases of DED were diagnosed among white adults and children compared with Asian and Black/African American patients; more cases were diagnosed among non-Hispanic and Latino children and adults compared with Hispanic/Latino patients, and more cases were diagnosed in patients in both age groups in the North Central and Northeast regions of the US.

Among the pediatric patients, DED had higher prevalence rates in those with refractive errors and eyelid/conjunctival disorders, the authors reported.

Regarding seasons, springtime had the highest prevalence of DED and winter the lowest among the pediatric population.

“Until recently, pediatric dry eye disease has been an under-recognized disease due to diagnostic limitations and challenges of interpreting the symptoms in children. We are excited about the potential for big data to provide insight that informs our care for this segment of the population,” Douglas and mentor Aisha Traish, MD, concluded.

Almost 5 million patients in the IRIS Registry had received at least one diagnosis of DED between 2013 and 2019; of those, 203,171 were children under 18 years of age and 4,592,808 were adults. 

IRIS Registry: Comparing dry eye disease in adult and pediatric populations

David Teenan, MD, from Optical Express, and colleagues reported that the safety and efficacy of the Tecnis Synergy intraocular lens (IOL) model ZFR00V indicates that it may be a good option for patients who desire meaningful gains in uncorrected visual acuity (VA) at all distances.

Teenan and co-authors Jan Venter, MD, and Stephen Hannan, MCOptom, conducted a study in which the participating patients completed a minimum of 1 follow-up visit within 1 year of the primary implant.

A total of 549 eyes were implanted with the IOL and 324 patients were available for analysis following implantation. The reported outcomes reflect the measurements obtained at the final evaluation following IOL implantation.

Teenan reported that 22% of patients had 20/16 uncorrected distance VA and 47% achieved 20/20; the respective intermediate percentages were 44% and 26%; and the respective near percentages for N4 and N5 vision were 50% and 34%.

The distance values represented a mean gain in 5 lines of VA the intermediate values a mean gain of 6 lines, and the near values a mean gain of 7 lines.

Regarding the postoperative refractive predictability, 80.9% of eyes were within 0.5 diopter (D) of the target refraction and 96.8% were within 1.0 D.

Thirteen eyes (1.5%) lost more than 2 lines of the best-corrected distance VA.

Complications included posterior capsular opacification in 3.3%, iritis in 2.9%, elevated intraocular pressure in 1.6%, cystoid macular edema in 1.6%, and blepharitis/meibomitis in 1.5%, Teenan reported.

Patient satisfaction was high with 80.0% of patients very satisfied and satisfied; 92.7% reported that they would recommend the IOL, and 89.1% would undergo the procedure again.

No difficulty was reported with glare by 40.0%, halos by 36.7%, starbursts by 54.6%, and ghosting by 72.7%. The respective percentages for patients reporting severe difficulties were 5.5%, 7.3%, 7.3%, and 1.8%.

The quality-of-life scores were high with 76.4% reporting no difficulties when engaged in hobbies and 85.5% when engaged in sports. A great deal of difficulty with hobbies was reported by 1.8%.

The investigators concluded that the safety and efficacy outcomes suggested that the lens may be a good alternative for patients looking for meaningful gains in uncorrected VAs at distant, intermediate, and near ranges.

Teenan said, “Over 9 in every 10 patients would recommend their procedure to friends or family.”

He advised that longer follow-up is warranted to better understand the comparative performance of this IOL.

Investigators reported that the safety and efficacy of the Tecnis Synergy IOL model ZFR00V indicates that it may be a good option for patients who desire meaningful gains in uncorrected visual acuity at all distances.

Continuous range-of-motion IOL scores high in patient satisfaction

Maria A. Guzman Aparicio, MD, and Teresa C. Chen, MD, from Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, found that pediatric patients have a significantly higher incidence of new-onset strabismus after tube shunt surgery for glaucoma compared with adults.

According to past literature, adults who undergo Ahmed (New World Medical) and Baerveldt (Abbott Medical Optics) tube shunt surgeries have postoperative strabismus 2% to 12.7% of the time after 1 to 5 years; in children, the percentages range from 3% to 4.2% with Ahmed valve surgery after 16 to 24 months of follow-up.

In their current study with longer follow-up periods, Guzman Aparicio and Chen sought to compare the frequency of strabismus after tube shunt surgery in the adult versus pediatric populations and to identify risk factors for strabismus after tube shunt surgery.

Their study included patients treated between September 1998 and September 2021. One surgeon performed all surgeries at 1 center. Pediatric patients were defined as those under 18 years of age and adults as those 18 years and older.

Patients were excluded if they had less than 6 months of follow-up or if they had concomitant major ocular surgery.

A total of 202 patients (223 eyes) were included, of whom 169 were adults (183 eyes) and 33 were children (40 eyes). The adults were a mean age of 63.6 years, and the children were 5.2 years. A total of 237 procedures were performed, 45 in children and 192 in adults.Average follow-up was 6.1 ± 4.8 years (range, 0.6 months to 20.1 years).

Among the 237 procedures, 4% of eyes underwent 2 or 3 tube shunt procedures. Ten percent of the eyes in the pediatric population, and 2.7% of the adult population were in this group.

Incidence of new-onset strabismus after tube shunt surgery

The determination of new-onset strabismus among a combined total of 172 adults and children without pre-existing strabismus indicated that 13% of pediatric patients had new-onset strabismus after a tube shunt procedure. This is in contrast to 0% of adults with new-onset strabismus after tube shunt surgery (at 6 months or at last follow-up).

The primary take-home messages from this analysis were as follows:

New-onset strabismus developed in 13% of pediatric patients vs. 0% of adult patients.

In pediatric and adult patients who had pre-existing strabismus, 100% continued to have strabismus after tube shunt surgery.

Risk factors for strabismus after tube shunt surgery were being a pediatric patient, being a pediatric patient with more than 1 tube placed, and having pre-existing strabismus.

Guzman Aparicio commented, “Before doing tube shunt surgery in children, it is important to educate parents of the possibility of new-onset postoperative strabismus in up to 13% of patients.” 

Chen emphasized, “Best surgical technique and implant choice may minimize the chance of postoperative strabismus. We hypothesize that our low rates of postoperative strabismus in adults may be due to putting glaucoma implants over instead of under the muscles and using Baerveldt 250 models over the 350 model.”

13% of pediatric patients had new-onset strabismus after a tube shunt procedure; in contrast, 0% of adults had new-onset strabismus after tube shunt surgery (at 6 months or at last follow-up).

Pediatric patients have higher incidence of new strabismus following tube shunt surgery than adult patients

 We're joined today with Dr. Roger Goldberg, who will be presenting this year from the podium at Academy. Welcome to you, Dr. Goldberg. Could you tell us a little bit more about your talk this year?

 Sure. I'm happy to be presenting some of the details from the YOSEMITE and RHINE clinical trials, and particularly that the arm of the trial where patients were treated with what's called a personalized treatment interval or variable interval, testing kind of the the efficacy and durability of faricimab, now known as Vabysmo, with a generic faricimab, for the treatment of diabetic macular edema.

Fariciamb, of course, is a bispecific antibody designed to inhibit both VEGF-A and Angiopoietin-2. And the YOSEMITE and RHINE trials were twin phase 3 studies, both very large over 900 patient trials, compaing faricimab given every eight weeks, faricimab, with this personalized treatment interval or PTI arm, which is basically kind of a treat-and-extend-based dosing regimen, where patients can be tested anywhere from every 4 all the way out every 16 weeks, based on both changes in the central subfield thickness on OCTs, so the amount of fluid on the OCT, as well as the visual acuity. And the comparator arm was aflibercept, dosed on label at a Q 8-week interval. All of these of course after a couple of loading doses.

Of course, the top line results from both YOSEMITE and RHINE is that faricimab showed excellent results the Q 8 or the PTI arm in terms of visual acuity gains and non inferior to on-label aflibercept. And the central subfield thickness, the OCT changes, again excellent results in both YOSEMITE and RHINE.

And the PTI arm in particular performed excellently both visual acuity wise and anatomic wise looking at the central subfield thickness.

And a lot of us, when we do treat-and-extend algorithms, although the visual acuity of courses is important, that is less consistent in our clinic, unlike in a clinical trial, where they use what's called best-corrected visual acuity, but we rely a lot of course on our exam and on what we see in the OCT. And here, I think it's really important that when we're looking at the efficacy and durability of faricimab, particularly in this PTI arm. How does it compare versus aflibercept? And couple different ways to look at that on OCT.

One is with what they call the absence of DME, which is the central subfield thickness less than 325 microns, or just throughout the macula, absence of intraretinal fluid. And across both of those measures, you know, kind of two different ways to try to quantify what we see on OCT, faricimab, both given every 8 weeks or the PTI arm, again, where patients can be extended up to 16 weeks, excellent results, and statistically better drying agents than aflibercept given every 8 weeks across both of those measures, absence of DME or absence of intraretinal fluid.

And that's really consistent importantly, basically across all time points after the loading period. And what that shows is that even with PTI being able to extend patients out all the way out potentially to 4 months, it's still kind of anatomically a better drying agent. So I think that was an exciting result for the PTI arm.

Now, the question of course, is, well, how many of the patients were able to be dosed at this extended interval, and if you look at the patients in this PTI arm, across both YOSEMITE and RHINE, we saw over three quarters of patients 78%, were able to go Q 12, or Q 16 weeks, so every three or four months. And of that, over 60% of both trials were able to go out to that 16-week interval, so well over half to 16 weeks, and over three quarters to 12 or 16 week interval.

So basically comparable in terms of visual acuity, frankly, better drying agent, and a huge proportion of patients able to go 3 months or longer between treatment. In fact, there was an option for patients to be dropped down into even monthly treatment. And at the end of year 2, there were about 10% of patients on a Q 4 week interval, 7% in YOSEMITE, 10% in RHINE, and that's kind of how the study ended in 2 years. We'll continue to follow these patients in the Rhone-X study.

The safety of faricimab, a very well tolerated, very comparable adverse event profile in the Q 8-week arm, in the PTI arm, and in the aflibercept Q 8-week arm, a safety profile, comparable of aflibercept and frankly, what we expect to see with intravitreal injections.

One of the other ways we tried to look at the kind of this treat-and-extend algorithm, the PTI, is with these heat maps, where it kind of follows every single patient and what their interval of dosing is. And what we see here is that kind of, there's already a huge swath of patients who are able to kind of quickly advance on a monthly interval, most of us do treat-and-extend in 2 weeks steps, but in the PTI arm, they actually were extended 4 weeks at a time. And so there's a big swath of patients are able to increase kind of straight away out to 16 weeks, expanding at 4 week intervals.

And then over time, we see kind of a, an increasing proportion of patients who are able to get out to 16 weeks over time. And then there is a cohort of patients on the order of about 20%, that do seem to have a more variable phenotype, they're able to go up a little bit, they're able to move back a little bit, and it's less consistent. And then of course, there's that very small kind of mid-single digit percentage that does require a Q 4-week treatment even with faricimab.

So I did share a couple of examples in the in the talk here, but obviously in this scenario, I won't be able to show them, but to summarize, the PTI arm really kind of simulates what we do in real clinical practice with treat-and-extend. The majority of patients, again, over three quarters, were able to get to Q 12 or Q 16 week intervals, they're able to kind of get there by week 52 and then maintain it out a year or 2, will actually continue to see further extension during the what's called Rhone-X extension studies, which continues to follow the YOSEMITE and RHINE patients.

And the safety was excellent, no cases of retinal vasculitis and so really shows the promise and potential of enhanced drying and extended durability. So all in all, really important clinical trial program. And I think many of us now have experience using it in the real world.

Roger A. Goldberg, MD, MBA, discusses his 2022 AAO poster: "T&E-Based Personalized Treatment Interval Dynamics in the YOSEMITE/RHINE Trials of Faricimab in DME."

YOSEMITE, RHINE treat-and-extend data show favorable results for faricimab for the treatment of DME

 polled our audience with the following question from September 18, 2022 to September 28, 2022:​ 

Are you planning to attend the AAO 2022 Meeting?

 and was promoted on Twitter, Facebook, and LinkedIn. Results show a majority of ophthalmologists plan to attend AAO in person.

21 responses were recorded, in total. Of these:

52% responded, "Yes, I will be there in person."

14% responded, "Yes, I will attend virtually."

33% responded, "No, I am unable to attend."

Results from our recent poll regarding AAO 2022 attendance indicate that most ophthalmologists and retina specialists plan to participate in the Annual Meeting in person in Chicago, Illinois.

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