In our seven-doctor retina practice we use a variety of imaging equipment; however, one of the constants is our reliance on spectral-domain optical coherence tomography (SD-OCT). Fifteen years ago, I was fortunate enough to train at the Tufts University/New England Eye Center with clinician-scientists who were instrumental in developing OCT technology. Now what stands out to me is the resolution we can obtain with SD-OCT, specifically the high-resolution SPECTRALIS multimodal imaging platform (Heidelberg Engineering, Inc.) is as good as that of our investigational devices from the early-to-mid-2000’s. I am eager to see where we will be in another 15 years.

Here I will overview our practice’s approach to managing diabetic eye disease.

Imaging is integral to the management of diabetic eye disease, therefore, all newly referred patients in our practice receive baseline imaging along with the clinical exam.

 What we do in the clinic should mirror, as best as possible, the best practices from randomized, controlled trials. Those lean heavily on angiography and especially OCT imaging to determine treatment selection and frequency. Therefore, baseline imaging almost always includes those two modalities at the minimum. We also, secondarily, may obtain ultra-wide color fundus photography (Zeiss and Optos platforms) in our offices where that technology is available.

The sequence of follow-up imaging is determined by disease severity and treatability, whether it be diabetic macular edema (DME), which is the most common manifestation of diabetic retinopathy (DR) which we treat, severe non-proliferative DR, or proliferative DR.

 Patients with disease for whom treatment is initiated we see more frequently to gauge their response.

The image registration we can obtain with SPECTRALIS is remarkable, and the TruTrack Active Eye-Tracking feature allows me to compare live images to understand progression. Rather than relying on maps, I prefer to scroll through the scans for a line-by-line comparison. This feature is especially helpful when initiating, changing, or adding treatment: for example, adding focal laser to an area of macular edema that is not responding to first-line anti-angiogenic therapy or adding a steroid for a patient who still has center-involving swelling despite frequent anti-angiogenic injections. When it comes to DME, we value the ability to objectively determine if treatment is providing a measurable improvement.

In the setting of proliferative diabetic retinopathy, I will occasionally perform repeat angiography; however, I generally do not repeat angiography frequently. Although overall, surgeons do less angiography than in the past, ultra-widefield angiography is important in the initial assessment of patients with suspected proliferative disease to ensure control and a complete laser pattern. In our practice, we use the Heidelberg Engineering Ultra-Widefield Module for that application in addition to other ultra-widefield platforms.

SPECTRALIS imaging is well tolerated by patients, and it can be done at any office visit. The patient remains seated in one spot while receiving OCT, angiogram, and ultra-widefield angiogram imaging at the same machine. Regardless of dilation status, we obtain a high-quality image, and the laser light wavelength is not overly bright as may be the case with other systems. For some widefield platforms, patients must be extremely dilated to obtain high-quality images and artifacts can be an issue. SD-OCT is by far the most utilitarian imaging modality available.

OCT and ultra-widefield color images play a key role in disease education, and I use them with all my patients to explain their disease process. In DME for example, I will show patients an example of a normal OCT versus their eye with a swollen macula. By seeing their image, they better understand their disease severity and how close to normal they are. Using the ultra-widefield color image, I point out the red dots that indicate DR explaining that they have bleeding in or in front of their retina and, depending on severity, that that may be treated.

I also love talking to patients about blood sugar control. I give all my diabetic patients one homework assignment: learn your hemaglobin A1c – whatever that number may be – and make a numeric goal with their endocrinologist or primary care doctor. Only about half of my patients know what their HbA1c is when they first come in. I tell them that blood sugar is the fuel for the diabetic fire; they can remove the fuel and put out the fire over time by controlling HbA1c. I explain that their disease comes from a combination of the duration and severity of their diabetes. I say, “if you have diabetes and intend to live—and see—for a long time, you must get your blood sugar under control to reduce your risk of vision loss.”

I am currently involved in a large initiative to democratize diabetic eye care by moving it into a non-traditional setting. Patient access and education are some of the biggest gaps in diabetes care. Repeated, patient-friendly messaging can go a long way to helping this significant public health problem. Diabetes is a US pandemic that preceded COVID-19 by many years and will be around long after COVID recedes. We must ensure that the approximately 50% to 60% of patients with diabeties who do not go to eye exams have a pathway to care and treatment.

 Having imaging that is high-quality, straightforward to obtain, and reproducible is a large part of their clinical care.

Diagnostic imaging is certainly required as part of the standard of care for managing diabetic eye disease. At the bare minimum, the physician must be able to obtain high resolution OCT images and high-quality angiograms to assess the initial anatomy and pathophysiology and to track treatment. Both of these we can perform with SPECTRALIS.

Eichenbaum is a partner in and director of Clinical Research, Retina Vitreous Associates of Florida in St Petersburg, Florida; a collaborative associate professor of ophthalmology at Morsani College of Medicine, University of South Florida, Tampa, Florida. Eichenbaum is a speaker for Genentech, Bayer, Allergan, Novartis, EyePoint, DORC, and Apellis; a consultant to Genentech, Regeneron, Allergan, Novartis, Alimera, Notal Vision, EyePoint, Gyroscope, Kodiac, RecensMedical, DORC, IvericBio, Apellis, KKR, Regenxbio, and Bausch + Lomb; an investigator with AsclepiX, Genentech, Regeneron, Bayer, Novartis, Opthea, Ocular Therapeutics, EyePoint, Mylan, Chengdu, Gemini, Gyroscope, Kodiac, NGM, RecensMedical, Alkahest, Ionis, IverisBio, Regenxbio and Unity; an equity/stockholder in Clearside, US Retina, Hemera Biopharmaceuticals, Boston Image Reading Center and Network Eye; and a founder of Network Eye.

1. Wong TY, Sun J, Kawasaki R. Guidelines on Diabetic Eye Care: The International Council of Ophthalmology Recommendations for Screening, Follow-up, Referral, and Treatment Based on Resource Settings. 

. 2018;125(10):1608-1622. doi: 10.1016/j.ophtha.2018.04.007.

2. American Diabetes Association. 10. Microvascular Complications and Foot Care: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018; 41 (Suppl 1):S105-18.

3. AAO. Sixty Percent of Americans with Diabetes Skip Annual Sight-Saving Exams. News release. Oct. 20, 2016. https://www.aao.org/newsroom/news-releases/detail/sixty-percent-americans-with-diabetes-skip-exams. Accessed Sept. 27, 2021.

Articles

SD-OCT is providing reproducible, high-quality, registered images to assess the treatment response in macular disease. 

High-quality, repeatable imaging is the cornerstone of managing diabetic eye disease

Fuchs endothelial corneal dystrophy is a progressive inherited condition that ultimately results in corneal edema and loss of vision. Up to now, treatment of patients with advanced disease involves corneal transplantation surgery. However, gene therapy may be a future option for these patients.

A team of investigators led by Hironori Uehara, MD, from the Phil and Penny Knight Campus for Accelerating Scientific Impact, University of Oregon, Eugene, and colleagues reported that CRISPR/cas9 prevented the disease in a mouse model.

The investigators reported their findings
in 

The problem in Fuchs’ dystrophy lies in a missense mutation in the 

 gene that leads to early-onset disease and progressive loss of vision resulting from edema and death of the corneal endothelial cells. Other mutations also are associated with Fuchs dystrophy, but the 

 missense mutant mouse model is the only one successfully created that has the key features of the disease.

In this mouse model, the investigators used a guide RNA targeting the start codon of the 

gene by non-homologous end-joint repair through CRISPR/Cas9. This approach blocked the gene expression at the translational level.

The strategy of targeting the start codon is sufficient for blocking gene expression at the translational level, which seemed a more direct approach than addressing targets farther downstream.

“The farther one targets downstream from the start codon, the greater the risk of missense mutations that result in viable mutant proteins with unknown activity. By targeting inside or near the start codon, this risk is minimized,” they explained.

“The results showed that intraocular injection of a single adenoviral vector achieved efficient and restricted delivery of CRISPR/Cas9 to adult post-mitotic corneal endothelium, leading to in vivo knockdown of the mutant 

 with long-term preservation of corneal endothelial density, structure, and function in the early-onset Fuchs dystrophy mouse model,” Uehara reported.

No adverse sequelae were observed on histologic evaluation or electroretinography images.

A major advantage of this gene therapy approach of COL8A2 start codon disruption is that no surgery is required to prevent vision loss in patients with early-onset Fuchs endothelial corneal dystrophy.

Another consideration is that because this treatment restored the phenotype in adult post-mitotic cells, the hope is that this method may be widely applicable to adult-onset diseases, the authors emphasized, even in tissues affected with disorders of nonreproducing cells.

The investigators commented on their results.

“This was the first study to demonstrate functional rescue with Cas9-mediated gene knockdown using start codon disruption. Future studies will explore the impact of this approach on endothelial and inflammatory gene expression using RNA-Seq and whether we can suppress activation of the unfolded protein response in endothelial cells.

In addition, prior to clinical development, gene therapy approaches will require optimization of gRNA and Cas9, understanding long-term effects, and refinement of the delivery strategy. Still, these results strongly suggest that our strategy can treat or at least prolong corneal endothelial life in early-onset Fuchs dystrophy, potentially eliminating the need for transplantation,” they concluded.

Uehara has no financial disclosures related to this content.

1. Uehara H, Zhang X, Pereira F, et al. Start codon disruption with CRISPR/Cas9 prevents murine Fuchs’ endothelial corneal dystrophy. eLife 2021;10:e55637; DOI: 

Successful treatment options can offer hope for patients with inherited disease. 

Investigators use gene therapy treatment of Fuchs in animal models

 (EYS) gene are the primary causes of retinitis pigmentosa (RP). RP25, a severe form of autosomal recessive RP, is seen in all ethnic groups with prevalence rates ranging from 5% to 33%, and patients who are affected early in life have no therapeutic recourse.

Francisco Diaz-Corrales, MD, PhD, Andalusian Center for Molecular Biology and Regenerative Medicine, Seville, Spain, and colleagues reviewed the knowledge about the effect of the 

Learning about autosomal recessive RP’s molecular mechanism has been hampered by the absence of a specific animal model for this human inherited retinal disease. Information about the protein’s cellular location and molecular features in different vertebrate animal models has provided some insight into the protein’s possible roles in the human retina.

Some things that are known is that the gene is the largest one in the human eye and extends for 2 Mb of genomic DNA in chromosome 6 (6q12.1-6q15). Studies disagree about the size of the 

 but both reported the gene is preferentially and abundantly expressed in human retina with minor expression in other tissues.

The size makes studying the gene difficult, Diaz-Corrales explained.

According to Diaz-Corrales, that difficulty arises from the complexity of the gene, which is divided into two distinct halves of the full-length EYS protein that likely have different roles and interactors.

“Shorter isoforms with just the epithelial growth factor (EGF)-rich or the Laminin G-rich sections will probably have particular localizations and functions, which will be relevant for analyzing and predicting the phenotypic impact of genetic variants,” Diaz-Corrales explained.

Affected patients generally begin to lose vision in the second and third decades of life; an early manifestation is night blindness and progressive constriction of visual fields. At a relatively young age, subcapsular cataracts can develop. The central vision generally is preserved until late in life.

Initially, fundus images show bone spicule pigmentation, pallor of the optic disc, retinal vessel attenuation, and a reduced or non-detectable electroretinogram response under scotopic and photopic conditions. With progression, thinning of the macula occurs. Fundus autofluorescence is helpful for determine the disease’s extent and diagnosis in cases with atypical presentation. In early-stage RP25, the peripheral ellipsoid zone is less visible, and the ellipsoid zone edge approximates the visual field along with disease progression.

Numerous mutations have been reported for EYS that include insertion, deletion, nonsense or missense substitution and splice site mutations, and these are manifested differently in different cohorts. However, truncating mutations lead to premature stop codons that remove laminin or epithelial growth factor domains, including frameshift and nonsense mutations.

Diaz-Corrales explained that because of the great variability in the severity of missense mutations and the lack of hotspots in EYS, identifying genotype–phenotype relationships is challenging. In addition, the full-length protein structure is divided into two distinct halves, as mentioned previously.

At 1 end is an N-terminal with a signal peptide followed by a stretch of EGF-like domains and a C-terminal rich in Laminin G domains interspaced with additional EGF-like domains at the other end. Different isoforms have been detected in the retina and other tissues. The diverse EYS isoforms, with particular domain composition and structure, perform specific roles depending on time, cellular compartment or tissue, complicating the analysis of the effect of mutations.

These can be gene/mutation-specific and those that exert a therapeutic effect apart from the genetic defect.

“Gene therapy can be applied in the early stages of degeneration when the retinal cells are impaired but the photoreceptor cells can be rescued by external genetic material,” he said.

The first gene therapy was approved to treat Leber congenital amaurosis caused by a defect in the 

. However, this approach may not work for EYS mutations because of the limited loading capacity of the viral vectors that hinders large gene delivery. A possible solution would be to use a reduced version of the gene to fit in the current vectors, i.e., a mini-

 with only essential information to prepare a protein to rescue the healthy phenotype.

Another gene therapy would be to use the gene(s) that substitute for 

 function in the murine retina and other species in which this gene is non-functional/absent once these factors are identified.

Additional methods for retinal delivery of transcripts exceeding 5 kb using the successful adeno-associated viral vectors (AAV) are theoretically feasible using dual AAV vectors. Transgenes approximating the size of the 

 transcript might be divided and co-infected in the same cell. To reconstitute the full-length transgene, possible mechanisms are trans-splicing through concatemerisation of AAV inverted terminal repeasts using donor and acceptor splicing sites or homologous recombination using sequence overlapping.

The limitations of these strategies depend on the efficiency of the specific splicing/DNA recombination events and frequency of generation of wrong concatemers.

A more recent technology proposed as a future treatment for many disorders caused by a genetic defect is the clustered regularly interspaced short palindromic repeats (CRISPR) system that edits the cell genome. Gene editing is a promising option for huge genes, because no exogenous gene has to be supplied to the diseased cells. Instead, their genome will be specifically modified to overcome the defect and produce a functional version of the protein. This technique has been successful in some blood cancers, but retinal evaluation remains preclinical.

Cell replacement is another option that may work for advanced retinal dystrophy to regenerate damaged cells. The cell sources can be either ocular-derived retinal progenitor cells or cells differentiated in vitro from embryonic stem cells or induced pluripotent stem cells.

For very advanced RP cases, prosthetics are another option. An electronic retinal implant, i.e., the Argus II epiretinal implant (Second Sight Medical Products), can provide artificial vision. This artificial vision can help some blind people to gain navigation autonomy after rehabilitation and training.

A more sophisticated approach is optogenetics, in which surviving retinal cells that are non-photosensitive are transformed to be light-sensitive via genetic modification.

Promising experimental results have been observed but clinical trials are needed. In Europe, the ongoing PIONEER phase I/IIa clinical trial (NCT03326336) combines optogenetics directed to remaining retinal ganglion cells using a light-amplification device.

Finally, intervening in the neurodegenerative process induced by RP is another possibility. Neuroprotection can extend photoreceptor life, delay the disease course, and increase the possible success of gene/cell therapy.

According to Diaz-Corrales, intrinsic difficulties associated with the study of EYS-retinopathy include the size of the gene and the absence of a mouse or rat animal model of the disease.

Diaz-Corrales has no financial disclosures related to this content.

1. Garcia-Delgado AB, Valdes-Sanchez L, Morillo-Sanchez MJ, et al. Dissecting the role of EYS in retinal degeneration: clinical and molecular aspects and its implications for future therapy. 

2021;16; https://doi.org/10.1186/s13023-021-01843-z

2. Abd El-Aziz MM, Barragan I, O’Driscoll CA, et al. EYS, encoding an ortholog of Drosophila spacemaker, is mutated in autosomal recessive retinitis pigmentosa. 

3. Collin RWJ, Littink KW, Klevering BJ, et al. Identification of a 2 Mb human ortholog of drosophila eyes shut/spacemaker that is mutated in patients with retinitis pigmentosa. 

Investigators believe the therapy could prove to be an option for the treatment of other retinopathies. 

EYS gene complexity key to treatment of retinitis pigmentosa 

Neurodevelopmental disorders (NDDs) are characterized by early-onset deficits of variable severity in personal, social, academic, or occupational functioning, as defined in the 

Diagnostic and Statistical Manual of Mental Disorders

 Developmental deficits may vary from very specific limitations of learning or control of executive functions to global impairments of social skills or intelligence.

Alterations in ocular movements and a large variety of visual problems have been associated with certain types of NDDs in children, which has lent support to the idea that the NDDs represent an etiological factor.

 Specifically, different types of accommodative, binocular, and oculomotor alterations have been reported in dyslexia, attention deficit/hyperactivity disorder (ADHD), and developmental coordination disorder (DCD).

Investigations carried out to date only suggest the potential for visual problems to be a comorbidity in these conditions, so it cannot be concluded that these alterations are causal factors. Indeed, one hypothesis proposes that the concept of dorsal stream vulnerability can be used to explain a cluster of problems that are common to many NDDs, including poor motion sensitivity, visuomotor spatial integration for planning actions, attention, and number skills.

To attempt to shed more light on the link between visual problems and NDDs, we recently conducted a clinical study to analyze the distribution of oculomotor and visual alterations, defined according to standard clinical tests in children with dyslexia, ADHD, and DCD (3 of the more common NDDs that can be examined easily in clinical practice). We compared the distribution with that obtained in healthy children without ocular pathology but with and without oculomotor anomalies.

We evaluated a total of 69 children (6 to 13 years old) in a prospective, nonrandomized comparative study, conducted at the Child Development Unit of the Alto Aragón Polyclinic in Huesca, Spain. All children were evaluated by an optometrist, an ophthalmologist, a speech therapist, a psychologist, and a neuropediatrician.

Among the children recruited for the study, 3 groups were clearly differentiated. These included a control group; healthy children with oculomotor abnormalities; and children with an NDD diagnosis. No comorbidity of NDD was present in any case.

A complete visual examination was conducted, including the measurement of uncorrected and corrected distance visual acuity; manifest and cycloplegic refraction; a cover test; a Maddox rod test; the measurement of near point of convergence (NPC); distance and near stereopsis; a Worth Four Dot Test; fusional vergence measurement; monocular and binocular accommodative facility; amplitude of accommodation; accommodative response at 40 cm (monocular estimation method); and a subjective evaluation of oculomotricity with the Northeastern State University College of Optometry (NSUCO) oculomotor test and the developmental eye movement (DEM) test.

An objective evaluation of oculomotricity was carried out with the eye tracker Tobii EyeX (Tobii) and Clinical Eye Tracker software (Thomson Software Solutions) in a subsample of 15 healthy children and 17 children with NDDs.

We found significantly worse near stereopsis in children with NDDs compared with healthy children (60.1 ± 71.2 vs 30.7 ± 23.9 in; 

 < .001) and in those with oculomotor abnormalities but without NDDs (60.1 ± 71.2 vs 30.8 ± 18.9 in; 

 = .001). Likewise, a significantly lower amplitude of accommodation was found in children with NDDs compared with healthy children in both the right eye (11.4 ± 2.8 vs 9.0 ± 2.0 D; 

 = .001) and the left eye (10.1 ± 2.8 vs 9.2 ± 1.9 D; 

No statistically significant differences between the groups were found in the measurement of near and distance phoria (

 ≥ .059). According to standard criteria, no statistically significant differences were present among the groups in the number of cases with binocular or accommodative disorders (

The comparison between the 3 types of NDDs included revealed the presence of a significantly lower amplitude of accommodation in children with DCD compared with those with dyslexia. Furthermore, less exophoria at near was present in children with dyslexia compared with children with ADHD
(

Concerning oculomotricity, significantly impaired scores were found with the subjective test (NSUCO and DEM tests) in children with NDDs compared with healthy children (

 < .001), with no significant differences between children with oculomotor abnormalities but without NDDs and children with NDDs (

 ≥ .063). Regarding eye tracking analyses, we found a significantly higher number of hypometric saccades in children with NDDs compared with healthy children (

A complete visual examination was conducted, including measurement of uncorrected and corrected distance visual acuity; manifest and cycloplegic refraction; cover test; Maddox rod test; measurement of near point of convergence (NPC); distance and near stereopsis; four-dot Worth test; fusional vergence measurement; monocular and binocular accommodative facility; amplitude of accommodation; accommodative response at 40 cm (monocular estimation method); and subjective evaluation of oculomotricity with Northeastern State University College of Optometry’s Oculomotor (NSUCO) and developmental eye movement (DEM) test.

An evaluation of oculomotricity was carried out with the Eye Tracker Tobii Eye X (Tobii) and the Clinical Eye Tracker software (Thomson Software Solutions) in a subsample of 15 healthy children and 17 children with NDDs.

Likewise, we found a significantly higher percentage of regressions in the group of children with NDDs when a time interval of presentation between stimuli of 1 second was used (

 = .012). Significant correlations were found between different NSUCO scores and percentage of regressions, number of saccades completed, and number of hypometric saccades.

Children with dyslexia, ADHD, and DCD show an altered oculomotor pattern and a more reduced amplitude of accommodation; however, this is not always compatible with the diagnostic criteria of an accommodative insufficiency. Accommodative and binocular vision problems are not always present in these children and so cannot be considered an etiological factor.

Hypometric saccades and regressions are commonly present in children with NDDs. However, oculomotor anomalies can be present in children with and without NDDs, and therefore they do not seem to be a good diagnostic criterion of these complex types of disorders.

Future research should be focused on the analysis of the impact of oculomotor alterations associated with NDDs and how complementary binocular and accommodative anomalies affect the child’s development. This is critical because it will help define a standardized scientific-based approach for the treatment of visual and oculomotor problems in children with NDDs. This, in turn, will help prevent exposure to pseudotherapies and treatments based on visual approaches that are not useful.

Bilbao is based at the Department of Optometry, Policlínica Alto Aragón in Huesca, Spain. She has no financial disclosures related to this content.

Piñero is part of the Optics and Visual Perception Group, Department of Optics, Pharmacology and Anatomy at the University of Alicante in Spain, and is based at the Department of Ophthalmology, Vithas Medimar International Hospital in Alicante. He has no disclosures related to this content.

Diagnostic and Statistical Manual of Mental Disorders (DSM-5)

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2. Posar A, Visconti P. Neurodevelopmental disorders between past and future. 

. 2017;12(3):301-302. doi:10.4103/jpn.JPN_95_17

3. Bilbao C, Piñero DP. Diagnosis of oculomotor anomalies in children with learning disorders.

. 2020;103(5):597-609. doi:10.1111/cxo.13024

4. Bilbao C, Piñero DP. Clinical characterization of oculomotricity in children with and without specific learning disorders. 

 2020;10(11):836. doi:10.3390/brainsci10110836

5. Molina R, Redondo B, Vera J, García JA, Muñoz-Hoyos A, Jiménez R. Children with attention-deficit/hyperactivity disorder show an altered eye movement pattern during reading. 

. 2020;97(4):265-274. doi:10.1097/OPX.0000000000001498

6. Hussaindeen JR, Shah P, Ramani KK, Ramanujan L. Efficacy of vision therapy in children with learning disability and associated binocular vision anomalies.

. 2018;11(1):40-48. doi:10.1016/j.optom.2017.02.002

7. Falkenberg HK, Langaas T, Svarverud E. Vision status of children aged 7-15 years referred from school vision screening in Norway during 2003-2013: a retrospective study. 

. 2019;19(1):180. doi:10.1186/s12886-019-1178-y

8. Mahone EM, Mostofsky SH, Lasker AG, Zee D, Denckla MB. Oculomotor anomalies in attention-deficit/hyperactivity disorder: evidence for deficits in response preparation and inhibition. 

. 2009;48(7):749-756. doi:10.1097/CHI.0b013e3181a565f1

9. Loe IM, Feldman HM, Yasui E, Luna B. Oculomotor performance identifies underlying cognitive deficits in attention-deficit/hyperactivity disorder.

. 2009;48(4):431-440. doi:10.1097/CHI.0b013e31819996da

10. Bucci MP, Brémond-Gignac D, Kapoula Z. Poor binocular coordination of saccades in dyslexic children. 

.2008;246(3):417-428. doi:10.1007/s00417-007-0723-1

11. Grisham D, Powers M, Riles P. Visual skills of poor readers in high school. 

. 2007;78(10):542-549. doi:10.1016/j.optm.2007.02.017

12. Kapoula Z, Bucci MP, Jurion F, Ayoun J, Afkhami F, Brémond-Gignac D. Evidence for frequent divergence impairment in French dyslexic children: deficit of convergence relaxation or of divergence per se? 

. 2007;245(7):931-936. doi:10.1007/s00417-006-0490-4

13. Atkinson J. The Davida Teller Award Lecture, 2016: visual brain development: a review of “dorsal stream vulnerability” – motion, mathematics, amblyopia, actions, and attention.

14. Braddick O, Atkinson J, Akshoomoff N, et al. Individual differences in children’s global motion sensitivity correlate with TBSS-based measures of the superior longitudinal fasciculus. 

. 2017;141:145-156. doi:10.1016/j.visres.2016.09.013

15. Bilbao C, Piñero DP. Objective and subjective evaluation of saccadic eye movements in healthy children and children with neurodevelopmental disorders: a pilot study. 

 2021;5(2):28. doi:10.3390/vision502002816.

16. Bilbao C, Piñero DP. Distribution of visual and oculomotor alterations in a clinical population of children with and without neurodevelopmental disorders. 

. 2021; 11(3):351. doi:10.3390/brainsci11030351

Investigators find that youth show altered ocular movements, reduced amplitude of accommodation. 

Link between neurodevelopmental disorders, visual problems studied

Micro-invasive glaucoma surgery (MIGS) has become a popular option for facilitating a reduction in intraocular pressure (IOP) when medical therapy has not adequately done so or is not a viable option.

These procedures involve various approaches including improving aqueous humor outflow through the trabecular meshwork (TM) or other components of the conventional pathway such as Schlemm’s canal. MIGS is less invasive and therefore poses a lower risk for complications than traditional glaucoma surgeries such as trabeculectomy and glaucoma drainage devices (tube shunts). 

However, MIGS does not always achieve target IOP. This presents a significant glaucoma treatment challenge, as every millimeter of mercury above target pressure represents an increased risk for disease progression and ultimately, vision loss.

Many surgeons believe that prescribing topical eye drops following MIGS will not deliver additional IOP reduction, particularly when the procedure has already targeted the diseased TM. My colleagues and I set out to test this hypothesis in one specific treatment scenario by comparing the IOP lowering effects of netarsudil ophthalmic solution 0.02% (Rhopressa, Aerie Pharmaceuticals) on eyes with previous Kahook Dual Blade (KDB) goniotomy versus goniotomy-naïve eyes.

KDB goniotomy (KDB, New World Medical), a common MIGS surgery, involves the removal of a small section of TM to create an opening into Schlemm’s canal to increase aqueous humor outflow. MIGS procedures that target the TM, including KDB goniotomy, experience a “floor effect” of IOP lowering due to their inability to further bypass episcleral venous pressure (EVP) and distal resistance in the conventional outflow pathway.

Netarsudil is a Rho kinase inhibitor that is thought to lower IOP through two primary mechanisms: 

1) increasing aqueous outflow through the TM cells, 2) reducing EVP.

 This MOA is unique compared to other available IOP lowering pharmacologic therapies. Dosed as one drop QD and prescribed typically as an adjunctive therapy, netarsudil has been shown to produce consistent IOP reductions across a range of baseline pressures.

Our retrospective chart review2 analyzed data on 50 eyes of 37 adult glaucoma patients treated with netarsudil at Mason Eye Institute at the University of Missouri in Columbia, Missouri between February 2017 and October 2020. The KDB group (n = 25) included adult glaucoma patients who had undergone KDB goniotomy with cataract surgery, then started on netarsudil with no additional eye surgeries.

Control eyes (n = 25) included those with history of cataract surgery but no goniotomy or any other angle surgeries, and were started on netarsudil for at least one month with no additional ocular procedures. 

The two groups had comparable baseline characteristics, including age, gender, ethnicity as well as type and severity of glaucoma, baseline IOP, and number of medications (all P≥0.05).

We defined the primary outcome as ≥ 20% decrease in IOP at the 1 month follow-up visit compared to the IOP measured at the time of netarsudil prescription. Secondary outcomes included adverse reaction to medication, and rate of medication discontinuation for any reason.

Upon completion of the analysis, we found that netarsudil had a significantly greater IOP lowering effect in eyes treated with prior KDB goniotomy compared to eyes without history of goniotomy.

This effect was independent of surgical outcomes of KDB goniotomy. Eighty percent of KDB-treated eyes achieved netarsudil treatment success (defined as minimum 20% IOP reduction) compared to 52.0% (13 out of 25) of control eyes (P = 0.037). Percent IOP reduction was 29.5±16.1% in KDB-treated eyes and 19.4±14.0% in control eyes (P=0.022).

Based on these results, which we presented at the American Glaucoma Society annual meeting, we hypothesize that netarsudil may facilitate additional IOP-lowering effects through its unique MOA, which targets EVP in addition to the trabecular meshwork. 

In KDB-treated eyes, the excision of TM at the nasal angle may allow for a greater concentration of netarsudil to travel downstream to the distal outflow system and act on episcleral veins to reduce EVP, producing a synergistic affect.

The overall rate of adverse reactions was 48.0%, most commonly reported as redness, allergy, and blurred vision. Consistent with previous studies, no adverse reactions were serious or vision-threatening, and all resolved upon discontinuation of the medication. The overall discontinuation rate was 58.0% with average treatment duration of 5.8 months prior to discontinuation.

Though adverse events led to some discontinuations, insurance-related challenges were the most common reason, as the timeframe in which these cases were treated includes a period prior to widespread coverage adoption of Rhopressa, which was the FDA approved in December 2017. Currently, 8 out of 10 insured patients have coverage for Rhopressa.


Contrary to a widely held perception, these data clearly indicate that patients who do not achieve a target IOP after an angle surgery such as KDB goniotomy may benefit from the use of netarsudil post-surgery. 

Though adverse reactions such as hyperemia are common, netarsudil is not known to cause any systemic side effects and is generally well tolerated. Continued improvement in insurance coverage makes this medication a viable option for many patients. Once-a-day dosing also helps to promote adherence.

Taking all of these factors into consideration and recognizing the critical importance of getting glaucoma patients to their target IOP, surgeons may want to consider prescribing this medication to patients with previous angle surgery to facilitate greater IOP reduction.

Of course, further research is needed to evaluate this and other combination approaches. As such, we are in the process of planning a randomized controlled trial to determine if this result is unique to the combination of KDB goniotomy and netarsudil therapy, or if additional IOP-lowering might be achieved through the use of other topical eye drops following various MIGS procedures.

An is an ophthalmologist in Bethesda, Maryland and is affiliated with multiple hospitals in the area, including University of Missouri Health Care-Columbia and Harry S. Truman Memorial Veterans Hospital. She received her medical degree from McGill University Faculty of Medicine.  Haochen (Emily) Xu, BA, contributed to this article. 


1. Tanna et al. Rho Kinase Inhibitors as a Novel Treatment for Glaucoma and Ocular Hypertension. 

2. Xu et al. Comparison of Response to Netarsudil in Kahook Dual Blade Goniotomy Treated Eyes and Goniotomy-Naïve Eyes. Poster presented at: The American Glaucoma Society Virtual Annual Meeting; March 4, 2021.

The unique MOA may deliver a synergistic effect when prescribed post-surgically.

Netarsudil provides IOP lowering in goniotomy treated eyes 

I was standing in the checkout line in my local grocery store and the time had come to pay for my comestibles. My preference is to purchase food items shortly before dinner, so I shop frequently—even daily—as they do in Europe and many other countries. It takes time, but the idea is that fresher ingredients almost always translates into a better meal.

My credit card was in my hand and I was about to insert it in the card reader when the lady behind the cash register asked “Would you like to make a donation for prostate cancer research?”

“Actually, I would like to make a donation for eye disease research. How do I do that?” I responded.

“Well, it seems to me that research into eye disease is extremely important,” I explained. “In fact, a recent survey of Americans revealed that we fear loss of vision more than we fear other diseases, including hearing loss and even cancer.1 Plus, when you think about it, everyone has eyes and is therefore at risk for eye disease, while only older men get prostate cancer. Thus, donations for eye disease research benefit everyone: men and women, young and old. Doesn’t that seem better than something that only benefits men?”

I was eager to know if my logic resonated with this store employee. “Who knows?” I thought to myself, “perhaps I can get this nationwide grocery store chain to start raising funds for eye research!” I waited to hear what she had to say.

It turns out that one of the job duties of department chairs these days is to raise funds, helping to support researchers and also medical student and resident teaching. And it just so happens that my counterpart in the Department of Urology in my medical school had wagered a bottle of wine that his department would raise more than my department. I began to imagine what might happen if I could convince this employee and her manager of the importance of vision research and start having the store ask people to support vision research when they pay. I began to think about what I might say to better get my point across.

The checkout lady looked at me quietly for a few moments. “Sir,” she said. “I just work here.”

Reading my mind, my friend who was in line with me touched my arm before I could go on with my argument. “Do not be obnoxious,” she said quietly. I looked at her, and then at the cashier, who looked relieved.

I inserted my credit card in the reader and paid my bill. “Have a nice day,” said the cashier. “You as well,” I replied.

1. Preidt, R; Blindness biggest fear for many Americans. August 4, 2016; WebMD, accessed October 6, 2021. www.webmd.com/eye-health/news/20160804/blindness-biggest-fear-for-many-americans

An experience at the grocery store serves as a reminder of the importance of fundraising for eye research. 

Fundraising for vision restoration

(RA-OCT) can provide high-quality volumetric retinal and optic nerve images of patients in the emergency department (ED), the findings of which correlated well with the clinical examinations, according to pilot study results presented at the Women in Ophthalmology 2021 Summer Symposium.

This technology has the potential to be useful in telemedicine, according to Eun Young (Alice) Choi, MD, and Anthony Kuo, MD, senior author and associate professor of ophthalmology at Duke University School of Medicine in Durham, North Carolina.

Evolution of optical coherence tomography of the human eye


Patients who present to the ED with ocular injuries may need to undergo a fundus examination, but there are scenarios in which that need may not be met for various reasons. For example, using RA-OCT may meet that need in remote areas.

In a pilot study, Choi and her colleagues tested the ability of RA-OCT to obtain remote fundus imaging of patients who presented to the Duke University ED with ocular complaints.

Six patients (3 men, 3 women; age range, 24-84 years) were recruited for the study over the course of 6 nonconsecutive days. Patients who presented with penetrating ocular trauma or loss of blood were excluded.

The swept-source OCT machine provided a 32° field of view of the retina, including the fovea and optic nerve head. 

Rectangular volumes and full-width B-scans were acquired in triplicate. Thickness maps were generated with semiautomatic segmentation of selected volumes.

The ophthalmology resident on call evaluated the patients and documented the imaging findings and diagnosis.

The clinician who operated the RA-OCT during imaging of 2 patients was positioned behind a Plexiglas barrier 6 feet away from the patients. 

Another 4 patients underwent imaging while the operator was in a separate room that was connected remotely to the RA-OCT via a local network.

A trained reader who was masked to the examination reviewed the OCT images, according to Choi.

The investigators reported that the images they obtained were of high quality and agreed with the clinical examinations. The documented pathologies included drusen and retinal thinning. In cases in which the retinal appeared normal, soft drusen were seen on OCT images.

Although the pathologies imaged in the pilot study were limited to findings in only a few patients, Choi envisions a future for RA-OCT in telemedicine.

RA-OCT is an investigational device being used under a research protocol. The device was developed by Joseph Izatt, PhD, of Duke Biomedical Engineering; Mark Draelos, MD, PhD, of Duke Biomedical Engineering and Surgery; and Ryan McNabb, PhD, of Duke Ophthalmology.


This article was adapted from Dr Choi’s presentation at the Women in Ophthalmology 2021 Summer Symposium, August 26-29, 2021, Amelia Island, Florida. Choi has no financial interest in this subject matter.

Ophthalmology Times: November 1, 2021

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