
This article was reviewed by Melinda Chang, MD

Artificial intelligence (AI) is slowly being integrated into ophthalmology and other medical fields.

“In machine-guided medical research, a specific research question is not needed as in traditional medical research, because the research can be data-driven,” said Melinda Chang, MD, an attending physician in the vision center at Children’s Hospital Los Angeles and an assistant professor of clinical ophthalmology at the Keck School of Medicine at the University of Southern California. “Analysis with machine learning can predict new data, identify new patterns, or learn the best action.”

AI, Chang explained, is useful in medicine for classification and prediction, for example, for classifying images as they correspond to diseased persons or controls.



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The technology can detect papilledema from fundus photographs and characterize visual function and ocular motility in nonverbal individuals via eye tracking, Chang said.

 in which 15,846 fundus photos (14,341 for training and validation and 1505 for external testing) were obtained with digital cameras at 24 centers nationally and internationally. 

An AI model was developed to classify the images as normal, papilledema, or a nonpapilledema abnormality of the optic disc.

The study found that the accuracy of the model for differentiating papilledema from nonpapilledema images was 87.5%, the sensitivity was 96.4%, and the specificity was 84.7%. When the accuracy was compared between normal images and those of any optic disc abnormality, the accuracy was 91.8%.

The study’s authors concluded that this model was most useful for identifying any optic disc abnormality and could be used in emergency departments or neurosurgery clinics to rule out papilledema without consulting with ophthalmology, Chang recounted.



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In an eye-tracking system, while a patient is viewing a visual stimulus on a computer monitor, an infrared camera records the corneal and pupillary light reflexes from each eye, which enables the direction of gaze to be calculated at any time point with high spatial and temporal resolution, she said.

Eye tracking has been studied to assess vision in nonverbal patients, eg, pediatric patients, those who are impaired neurologically, and those with developmental disorders.Its capabilities in visual rehabilitation and for measuring the degree of strabismus also have been assessed. 

Chang focused on children with cortical visual impairment (CVI), ie, vision loss due to damage to the post-geniculate visual pathways in the brain.

“This is the most common cause of pediatric visual impairment in the US and developed countries,” she said.



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CVI risk factors include prematurity, hydrocephalus, seizures, hypoxic ischemic encephalopathy, and other neurologic conditions.

Children with CVI have visual deficits that may differ from children with ocular causes of visual impairment. 

For example, CVI causes more difficulty with low contrast; motion sensitivity may be spared in some children with CVI; and when in environments that are visually complex, children with CVI may have more difficulty seeing, she explained.

“Having an understanding of these unique visual deficits is important when guiding therapy. We know that these patients have the capacity to improve over time, but the factors that drive improvement are unclear,” Chang said.

Visual stimulation therapy is widely used, but no controlled trials have been conducted to assess the efficacy of visual stimulation.

“Establishment of an objective method for assessing visual stimulation (and other therapies) is important for pediatric patients with CVI,” she emphasized.



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Chang demonstrated patterns of fixation in children with CVI using these technologies. A child who served as a control was seen to be fixating on a baby’s eyes and hands in a brightly colored photo of that baby in a ball pit. 

In contrast, a child with CVI was seen to be fixating mostly on the brightly colored balls with fewer fixations on the baby’s face in the same photo.

“The child with CVI appears to prefer looking at bright colors rather than faces,” she commented.

Problems with low contrast were demonstrated in a second substantially darker photo in which a child with CVI fixated only once on a low-contrast object (bird) compared with a normal child who focused numerous times on a low-contrast human face in addition to the bird.

Another type of visual deficit was demonstrated in a photo with a highly complex background in which a child with normal vision had many fixation points in contrast to a child with CVI who had no fixation points within the complex image; the child with CVI had many more fixation points when the picture was significantly simplified with a plain background. 



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“These findings demonstrate the crowding effect in CVI, in which vision is worsened by visually complex scenes and distractors,” Chang explained.

Without machine learning, Chang and associates were able to do simple analysis to determine that children with CVI had several visual deficits compared to controls, such as decreased contrast sensitivity and increased saccadic latency. 

The investigators will use AI combined with eye tracking to identify other visual and oculomotor abnormalities, and potentially identify new deficits specific to CVI.

“The model will help determine the relative importance of various features such as color, background, faces, motion, and contrast, among others, in facilitating vision in children with CVI,” she said.


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Any information gained from such an analysis will help identify therapeutic targets and features that can be used to monitor disease severity and treatment efficacy.

“AI is a powerful tool with the potential to automate image analysis for neuro-ophthalmic conditions. Eye tracking facilitates visual assessment in nonverbal individuals, including children with CVI,” Chang concluded. 


e:mchang@chla.usc.edu
Chang has received grant funding from th

e Children’s Eye Foundation of AAPOS and the Knights Templar Eye Foundation.


1. Milea D, Najjar RP, Jiang Z, et al. Artificial intelligence to detect papilledema from ocular fundus photographs. 

. 2020;382:1687-1695. doi: 10.1056/NEJMoa1917130

Articles

Technology with potential to improve treatment and evaluation of cortical visual impairment.


Cutting-edge neuro-ophthalmology: Combining artificial intelligence, eye tracking

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This article was reviewed by Savak Teymoorian, MD, MBA

Early experience with the new intracameral bimatoprost 10-μg implant (Durysta, Allergan) in clinical practice indicates that it is a valuable addition for treating patients with ocular hypertension and 

, according to Savak Teymoorian, MD, MBA.

“Our aim in managing patients with ocular hypertension and glaucoma is to control their IOP so as to mitigate disease progression without adversely affecting quality of life,” said Teymoorian, a cataract and glaucoma specialist at Harvard Eye Associates in Orange County, California.



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“In deciding on our interventions to achieve that goal, it is necessary to balance the risks and benefits of each treatment option. It is clear to me that with its IOP-lowering efficacy and ability to address the drawbacks associated with topical drops, the benefits of the sustained-release prostaglandin significantly outweigh any risk associated with its administration.”

® that he implanted the bimatoprost product into approximately 55 eyes within the first month of using it. 

The satisfaction shared by patients is something novel in the glaucoma segment of his practice and is rewarding.

“Ophthalmologists who perform cataract surgery are used to seeing patients who are extremely happy because of the outcomes of their procedure, but gratification is rare among patients being treated for glaucoma. The recipients of the bimatoprost implant, however, are extremely happy because they have been able to eliminate or reduce their topical medications and the inconvenience, [adverse] effects, and cost associated with their use,” he said.


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Adherence with topical medications is well recognized as a key barrier to successful management of glaucoma. The issues underlying Adherence are multifaceted, Teymoorian said.

“Noncompliance can occur because of a plethora of factors. Some patients do not get their prescription filled, some don’t remember to use their medications, and some do not instill them properly,” he explained.

“The ability to take the responsibility for treatment away from the patient is one of the reasons why the minimally invasive glaucoma procedures have done so well. The value of the bimatoprost implant is similar in that regard,” he added.

The ability to reduce ocular surface toxicity from topical drops is another benefit of the bimatoprost implant.

“Minimizing or eliminating the number of topical medications a patient is using allows the ocular surface condition to improve. As a result, patients are more comfortable, their vision is better, and they can also eliminate or reduce their need for artificial tears and any other medications that they are using to manage dry eye signs and symptoms,” he said.


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Patients who are on topical medications for IOP-lowering, regardless of where they are on the continuum of glaucoma severity, may be considered as candidates for the bimatoprost implant. 

However, Teymoorian noted that so far he has selected patients who are taking a topical prostaglandin analogue and who are pseudophakic in particular because they will likely have a deep anterior chamber, enabling safe and proper placement of the implant, and cataract development will not be an issue.

“My accumulating experience with the product is reinforcing its efficacy, safety, and benefits. The more I see how it allows me to discontinue all or some topical medications and how happy patients are, the more I am willing to offer the implant to patients,” he explained.



The implantation procedure should be done with the eye topically anesthetized and under aseptic conditions. 

Depending on their comfort level and facility, clinicians can choose to perform the procedure either in a surgery center using an operating microscope, or a slit lamp in an in-office procedure room.



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When injecting the bimatoprost implant in the surgery center where the patient is lying under the microscope, Teymoorian said he has the patient’s head tilted up at about 30° and asks the patient to sit up immediately after the injection as these positions promote settling of the implant into its targeted location in the inferior angle.

“It has been remarkable to me that as soon as the injection is done, patients note how easy it seemed, tell me that they felt nothing, and ask when can they have the second eye procedure,” Teymoorian said. “I take these as signs that the procedure is well tolerated. The key is to make sure the patient is comfortable.”

Changes to existing topical medications and scheduling of the first postinjection follow-up visit are individualized, taking into account medication burden and glaucoma severity. 

Patients on a topical prostaglandin alone or a topical prostaglandin plus one adjunctive medication whose IOP has been well controlled may have both agents discontinued if they have mild-to-moderate glaucoma, and they will likely be asked to return 7 to 10 days postinjection.



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Patients with more severe disease and on multiple medications are seen within a few days after the procedure and are weaned more slowly off existing topical drops according to the level of their IOP.

“Initially I thought the implant would be something that could simply replace a topical prostaglandin. However, as I treat more patients who are on multiple medications, I am realizing that some can do very well being taken off more than just the prostaglandin,” Teymoorian said. “The experience with patients who can stop multiple medications highlights the efficacy of the implant and also the problem of noncompliance for patients who are on topical drops. Clearly, even those individuals who are well intentioned may not be administering their medications properly.”



The implant is approved for one-time administration. Clinical trial experience indicates that the IOP-lowering benefit can last from 4 months to 2 years or more, and research is underway to collect data that will support FDA approval for repeat injections.

“Ongoing management for patients who begin to lose the IOP-lowering effect from the bimatoprost implant is something that we will need to address in the future,” Teymoorian said. “But while we think about what we might do tomorrow, we need to plan and execute for today. Even if I think it is a one-time treatment for now, I find no reason to hesitate using the implant in appropriate patients when I consider its many benefits and minimal risk.”



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Anticipating the opportunity for repeat injections, he noted it is exciting to think that early treatment with the bimatoprost implant holds promise for preserving vision and quality of life for glaucoma patients over the long term.

Teymoorian concluded that, in theory, disease control should be much better for patients who are being treated with the implant than for those who are on topical therapy because the implant ensures consistent medication delivery, while with topical treatment clinicians have to assume patient adherence.

“Consistently effective IOP control increases the likelihood that we will be able to slow or even halt glaucoma progression,” he said.


Teymoorian is a consultant, speakers’ bureau member, and investigator for Allergan.

Sustained release helps mitigate disease progression without impacting quality of life.


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This article was reviewed by Jesper Høiberg Erichsen, MD



Results of a prospective randomized trial comparing 5 medication regimens for controlling inflammation early after uncomplicated surgery show that beginning monotherapy with a topical nonsteroidal anti-inflammatory drug (NSAID) the day of surgery offered the best outcome for efficacy and safety.

The findings, presented by Jesper Høiberg Erichsen, MD, revealed that adding a topical steroid to the NSAID provided no benefit but could adversely affect intraocular pressure. 


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Initiating topical treatment 3 days preoperatively also conferred no advantage for better inflammation control, whereas a dropless approach using a sub-Tenon corticosteroid injection proved inferior to topical treatment. 

“Controlling postoperative inflammation is important for achieving a successful outcome after cataract surgery. Surgeons generally prescribe an anti-inflammatory prophylactic regimen parallel to surgery, and recent meta-analyses have documented a beneficial effect of using a topical NSAID,” said Erichsen, a doctoral student in the Department of Ophthalmology at Rigshospitalet-Glostrup in Denmark. 

He added that several questions about inflammation prophylaxis require investigation.

“Based on our results, we recommend that cataract surgeons consider using NSAID monotherapy as anti-inflammatory prophylaxis in uncomplicated cases,” he said.

Patients with a senile cataract were eligible for enrollment in the study if they were undergoing uncomplicated surgery and had no history of diabetes, uveitis, glaucoma, retinal vein occlusion, epiretinal membrane, retinal detachment, or advanced age-related macular degeneration. 


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A total of 470 patients were randomly selected in 5 equal groups to receive topical prednisolone and ketorolac started 3 days preoperatively, topical prednisolone and ketorolac started on the day of surgery, ketorolac started 3 days preoperatively, ketorolac started on the day of surgery, or a sub-Tenon depot of dexamethasone 2 mg/0.5 mL. 

All topical drops were to be administered 3 times daily and continued for 21 days after surgery.

After random selection, 14 patients were excluded, and 438 completed follow-up to the primary end point visit at postoperative day 3. The mean age of the 456 patients included in the baseline data analysis was 72 years, and almost two-thirds of the participants were women.

The primary outcome assessed change from baseline in anterior chamber flare measured on undilated pupils using a flare photometer (Kowa FM-600, Kowa Company). 

For statistical analyses, the group that received the combination topical regimen started preoperatively was used as the control group.



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Median flare was 10.1 photon counts per millisecond at baseline in all groups, and it increased significantly at postop day 3 in all groups. 

The greatest rise occurred in the dropless group, and the difference in change from baseline compared with the control group was statistically significant only in the dropless group.

“As another interesting result, we found that only a few patients in the topical treatment groups [1.1%-3.4%] needed additional intervention to control inflammation, whereas more than one-third of patients in the dropless group needed rescue anti-inflammatory treatment,” Erichsen said. “Minimizing the need for topical drops is desirable in older patients who may struggle with administration, but the dropless approach using the sub-Tenon injection did not seem effective for achieving that goal.”

Anterior chamber cell count at postop day 3 was investigated as a secondary outcome measure. The mean value was 3.4 in the control group, ranged from 3.8 to 4.1 in the 3 other topical regimen groups, and was 5.5 in the dropless group. 

Again, Erichsen noted that the only the difference between the dropless and control groups was statistically significant.


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Postop day 3 logMAR visual acuity measured with Early Treatment Diabetic Retinopathy Study charts was also evaluated as a secondary end point.

The results showed no significant differences between groups.

Intraocular pressure, another secondary outcome measure, was found to decrease significantly after cataract surgery in all groups. 

However, the drop was significantly less in the combination treatment groups that received a topical steroid compared with those receiving a topical NSAID alone and the dropless group.

Erichsen initially made his presentation at the virtual Association for Research in Vision and Ophthalmology 2020 annual meeting. 



Neither Erichsen nor any of his coauthors has any relevant financial interests to disclose.

Large randomized trial compares efficacy and safety of multiple regimens

Ophthalmology Times: October 15, 2020

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Long-acting prostaglandin implant creating shift in IOP-lowering therapy

Minimize inflammation after cataract surgery