Cheryl Guttman Krader is a contributor to Dermatology Times, Ophthalmology Times, and Urology Times.

Cheryl Guttman Krader, BS, Pharm

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The potential mechanisms by which mass distribution of azithromycin improves health and childhood mortality and its effects on both human microbiomes and antimicrobial resistance were discussed recently by Thuy Doan, MD, PhD.

“As of 2020, approximately 1 billion doses of azithromycin [have been] distributed worldwide for trachoma elimination,” Doan said. “It is now proven that mass distribution of azithromycin to preschool children improves childhood mortality [rates]. Furthermore, azithromycin is one of the most-prescribed oral antibiotics in the United States, and it was the No. 1 prescribed antibiotic worldwide to patients with SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2] infection at one point during the pandemic.”

Doan is director of the Ralph and Sophie Heintz Laboratory, Francis I. Proctor Foundation, at the University of California, San Francisco.

Doan pointed out that the effects of mass distribution of azithromycin are long-lasting.

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“In a series of studies, we have shown that mass drug distribution affects the microbiomes of the ocular surface, nasopharynx, and gut,” Doan said. “It decreases the pathogen load in the gut, particularly 

 species, and the alpha and beta coronaviruses in the nasopharynx.”

Doan noted that azithromycin alters the structure of the ocular surface microbiome and the bacterial community diversity of the ocular surface.

“Not surprisingly, we found that mass distribution of azithromycin for 2 years increases macrolide resistance determinants in the gut, but it does not affect the resistance determinants of other classes of antibiotics in the gut,” Doan said.


The first evidence that mass distribution of oral azithromycin in a trachoma-endemic area reduced mortality in children came from a randomized study conducted in Ethiopia led by Thomas M. Lietman, MD. 

The benefit was confirmed in the MORDOR study, which was a larger scale investigation run by the Proctor Foundation, sponsored by the Bill and Melinda Gates Foundation. It involved communities in 3 sub-Saharan African countries.



Ocular manifestations of mycoplasma-induced rash and mucositis



According to Doan, the reduction in childhood mortality with mass azithromycin treatment could be partly attributed to the antimicrobial activity of the antibiotic, which led to reduced rates of malaria, dysentery, meningitis, and pneumonia.

Studies of the effects of mass distribution of azithromycin on the human microbiome were undertaken after analyses of conjunctival, nasopharyngeal, and rectal swabs from a subgroup of children in the MORDOR study identified microbiome changes. 

The analyses focused on the top 15 genera of bacteria in the gut identified by RNA deep sequencing and evaluated changes after 4 biannual distributions of azithromycin and placebo.

 load at baseline between treatment arms, but there was a reduction in 

 at the genus level in the gut microbiome of children treated with azithromycin at 24 months. 

was significantly more abundant in the control group compared with children who received azithromycin. 

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The findings were replicated in an individual randomized controlled study conducted in another sub-Saharan country.

“These results make sense because we know 

infections could potentially result in mortality by causing dysentery and malnutrition,” Doan said. “Taken together, they suggest that 

 likely play an important role in childhood health in sub-Saharan Africa.”

The investigators also evaluated the role of viral infections in childhood mortality by using RNA deep sequencing to interrogate the nasopharyngeal virome.

“In this study we were surprised to find a relative reduction in coronavirus both at the genus level and also at the species level in villages [where individuals] were treated with azithromycin,” Doan noted.

“The significance of these findings escaped us until the beginning of 2020 when we started to hear about outbreaks of respiratory distress syndrome in China that were associated with a novel coronavirus now known as SARS-CoV-2.”

Investigating the low vulnerability of posterior eye segment to SARS-CoV-2

The coronaviruses isolated from the African children belong to the same genus as SARS-CoV-2 and are known human pathogens reported to cause respiratory tract infection, meningitis, and gastroenteritis in children.

“These particular viruses generally cause self-limiting diseases, although deaths have been reported in children and immunocompromised patients,” Doan said. “Although we do not know if clinical severity depends on viral load and our study was not designed to study the effect of the virus in childhood mortality, we do know that treatment with azithromycin was associated with a reduction in coronavirus levels. The change in the virome is intriguing, as we do not expect antibiotics to affect viruses. This may be a unique property of azithromycin.”

Evaluation of the biospecimens from conjunctival swabs showed that azithromycin treatment also altered the structure of the ocular surface microbiome, at least at the community level, Doan said.

Comparisons between the placebo- and azithromycin-treated children showed that the density distribution of the ocular surface microbiome was similar at baseline in the 2 groups but differed significantly after 24 months of treatment because of increased diversity in the azithromycin group.

“Generally, we associate an increase in diversity with health, whereas a decrease in diversity is associated with disease,” Doan said.

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Accompanying the practice of mass antibiotic distribution is the concern that it will promote selection of bacteria resistant to the specific class of antibiotic and to other classes. 

This issue was addressed by evaluating resistance gene expression of 

 isolated from the nasopharynx and of gut bacteria sequences from rectal swabs.

Focusing on the results for the gut, Doan reported that after 4 biannual distributions, the prevalence of macrolide resistance gene expression was increased significantly among children residing in villages who received azithromycin compared with placebo. However, coresistance of other classes of antibiotics was not detected.

Doan delivered the Jones/Smolin Lecture at the American Academy of Ophthalmology’s virtual 2020 annual meeting. Doan has no relevant financial interests to disclose.

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The Tecnis Synergy and Tecnis Synergy Toric II

 (Johnson & Johnson Vision) received FDA clearance in early May 2021 and are now commercially available in the United States.

As an early adopter of these new implants, which are designed to provide a continuous range of vision, Eric D. Donnenfeld, MD, said that he is extremely pleased with the outcomes he has achieved during his initial experience.

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“The optic of the Synergy IOLs is very interesting, as it combines trifocal and extended depth-of-focus [EDOF] designs and brings the benefits of both technologies to give patients a full range of quality vision,” he said. “In particular, the Synergy IOLs stand out for providing an improved level of near vision.”

Overall, Donnenfeld said the IOLs seem to give the highest likelihood of achieving spectacle independence of any currently available presbyopia-correcting IOLs.

“I have had the opportunity to use the Synergy IOLs for about 1 month, and I am looking forward to gaining more experience and seeing the outcomes in a larger group of patients and after longer follow-up,” he said.


The near vision benefit of the Synergy IOLs is particularly impressive, according to Donnenfeld, founding partner of Ophthalmic Consultants of Long Island and Ophthalmic Consultants of Connecticut, Garden City, New York, and clinical professor of ophthalmology at New York University Medical Center, New York.

“Patients [in whom] I have implanted the Synergy IOL are reading J1 effortlessly, even in situations with moderate lighting,” he noted. “Achieving that level of near vision with other IOLs usually requires an abundance of light.”

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Distance vision with the Synergy IOL is comparable to that of trifocal IOLs, and with the Synergy IOL there is no drop-off in visual acuity or quality in the intermediate range.

“Patients implanted with the Synergy IOL have experienced no problems with driving nor concerns with driving at night,” Donnenfeld said. “They still may notice some halos around lights, which would be expected with any diffractive trifocal design, but the halos are not bothersome. I have not had any patient complain.”

The novel optic design of the Synergy IOL also seems to explain another interesting feature of the lens that sets it apart from other IOLs.

“Results from bench testing showed that contrast sensitivity performance was better with a large aperture and dim illumination than in bright light with a smaller aperture size,” Donnenfeld explained.

The Synergy IOLs incorporate technologies for violet light–filtering and chromatic aberration improvement that may reduce dysphotopsias and improve contrast and visual clarity.

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Donnenfeld observed that the features of the Tecnis Synergy IOL optic suggest that the visual outcome should be forgiving to small amounts of decentration or residual refractive error.

The Tecnis Synergy IOLs are made of the same hydrophobic acrylic material found in other Tecnis lenses and have the same A-constant as the Tecnis monofocal (ZCB00) and Tecnis Eyhance IOLs.

“The Tecnis IOL hydrophobic acrylic material is glistening free and provides crisp quality vision," Donnenfeld said.

Donnenfeld said he expects that the Tecnis Synergy IOLs will be an extremely valuable addition to existing presbyopia-correcting IOL options. He noted he has also been very happy with the Tecnis Eyhance IOL (Johnson & Johnson Vision) and the AcrySof Vivity IQ (Alcon) IOLs that are now available.

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“Both of these IOLs give patients some improved near vision without compromising the quality of distance vision because there is no loss of contrast at distance,” he said.

Donnenfeld said he is still fastidious about selecting appropriate candidates for a trifocal IOL.

“I am very comfortable recommending the Synergy IOL to a broader pool of patients, but at the same time, I am still very careful about evaluating patients for conditions that can affect the outcome, such as significant dry eye disease and macular pathology,” he explained.

Trifocal and EDOF IOLs available in Europe are expected to enter the US market. However, the next big advance in presbyopia-correcting IOLs will come with the approval of an accommodating IOL, Donnenfeld said. The Juvene (LensGen) may begin investigation in a phase 3 trial in 2021.

“I had the opportunity to implant this fluid-optic IOL in Mexico and was impressed by the quality of vision it provides,” he concluded. The Juvene IOL gives true spectacle independence without light splitting. It offers the range of vision of a trifocal IOL with the contrast sensitivity of a monofocal lens,” he said.


Donnenfeld is a consultant for Alcon, Johnson & Johnson, and LensGen.

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Findings of a retrospective, comparative cohort study demonstrate benefit for integration of spectral-domain 

 in a diabetic retinopathy (DR) telemedicine screening program.

Lloyd P. Aiello, MD, PhD, presented study data from 422 eyes of 211 patients with diabetes who were consecutively imaged between January 8 and March 16, 2020, using the commercially available platform Monaco (Optos), which allows SD-OCT and UWF imaging in a single sitting. 

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Participants were seen in a UWF image-based DR teleophthalmology program at Joslin Diabetes Center in Boston, Massachusetts.

The results showed that the dual imaging substantially increased detection and reduced false positive assessments of 

“Given the reduced effort, compact footprint, and reduced overall cost of integrated SD-OCT/UWF devices, their use in large DR screening programs could substantially improve disease identification and reduce unnecessary referrals,” said Aiello, a professor of ophthalmology at Harvard Medical School and director of the Beetham Eye Institute of Joslin Diabetes Center.

“However, it should be noted that this study only evaluated 422 eyes and all images were evaluated in a centralized reading center using standardized protocols,” he said. “Thus, the applicability of the findings in other settings is unknown.”

measurements for the Monaco instrument is pending, the OCT images were evaluated qualitatively using a standardized template. 

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Each scan was evaluated for macular pathology, including looking at the foveal contour and looking for macular edema, ERM, signs of macular degeneration, and other macular diseases. 

The UWF graders were masked to the OCT images and OCT findings, and graders evaluating the SD-OCT images were masked to the UWF images.

The 211 patients included in the study had a mean age of 53.5 years. Based on UWF grading, DR was absent in 58% of eyes and 93% of eyes had no DME. 

Eyes with DR spanned the spectrum of severity, but the distribution was weighted toward less severe disease with most eyes having mild nonproliferative DR. 

Sixty eyes (14.2%) were graded as having referrable DR, which was defined as moderate nonproliferative DR or worse or any level of macular edema.

With UWF imaging, less than 1% of eyes were ungradable for determining DR severity and less than 1% were ungradable for determining DME presence. For both modalities, less than 1% were ungradable for overall macular pathology.

Macular pathology was identified by UWF in 8.1% of eyes and in 13% of eyes by 

Noninvasive angiography with OCT offers definite value

DME was the most commonly identified pathology on UWF imaging (75%) but accounted for only 36% of macular disease identified by OCT. ERM accounted for 29% of macular pathology on UWF imaging but 52.7% of macular disease by 

Comparisons between the UWF and SD-OCT gradings showed good agreement when the determination was that DME was not present—when UWF imaging alone found DME was not present, SD-OCT found 

in only 1.5% of those eyes. 

When the UWF image grading identified DME present, the determination was not confirmed by SD-OCT in 75% of those cases.

“Overall, UWF image grading suggested that

 was present in 4.7% of eyes, [whereas] grading by SD-OCT determined DME was present in only 2.1% of the cohort,” Aiello explained. “Thus, UWF alone had low sensitivity and low positive predictive value for DME detection, but high specificity and high negative predictive value compared [with] SD-OCT.”

The results were similar in considering detection of clinically significant macular edema (CSME), although the sensitivity of UWF was even lower for this diagnosis. 

Approximately 27% of eyes with CSME present on SD-OCT were identified by UWF imaging alone.

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ERM was detected by UWF image grading in 2.4% of eyes and by SD-OCT in 6.8% of eyes. Only 3.4% of ERMs detected on SD-OCT images were identified on UWF imaging alone. 

When UWF

 alone found ERM was absent, SD-OCT found an ERM in 6.8% of eyes. When UWF grading showed that ERM was present, however, only 10% of those cases were confirmed by SD-OCT. 


This article is based on a presentation made at the Association for Research in Vision and Ophthalmology’s virtual 2021 annual meeting. Aiello is a consultant to Optos but is not paid for his services.

Dual imaging may reduce costs, unnecessary referrals, telehealth study results show.

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Results from 5 years of follow-up show that minimally invasive glaucoma surgery (MIGS) with simultaneous implantation of 2 trabecular microbypass stents (iStent Inject, Glaukos) combined with phacoemulsification is safe and provides durable moderate lowering of IOP. 

It also reduced the burden of topical ocular hypotensive medications, according to Karsten Klabe, MD.

“A number of MIGS procedures are now available, and [although] they have shown encouraging initial results in premarketing clinical trials, data are needed to understand their long-term efficacy and safety,” said Klabe, who is in private practice at Breyer Kaymak and Klabe Augenchirurgie in Düsseldorf, Germany, and is a partner at International Vision Correction Research Center of the Universitäts Heidelberg-Augenklinik.

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“Our experience using combined iStent Inject implantation and cataract surgery shows that with selection of appropriate candidates, only rare patients will need further intervention for their glaucoma, and the majority can become medication-free,” he said. “Considering the latter benefit, adding the iStent Inject when patients need cataract surgery addresses the adherence issues we face when prescribing glaucoma therapies and their potential to cause ocular surface disease so that patients have a higher quality of life.”

The 2 microstents are injected into the eye using a specially designed applicator. 

Klabe’s study of outcomes after combined cataract surgery with implantation of the iStent Inject was a retrospective review that included 164 eyes of 103 patients. 

The cohort had a mean age of 75.4 years and the majority were male. 

Primary open-angle glaucoma was the predominant diagnosis (82%), and the remaining eyes had pseudoexfoliation glaucoma (18%).

Preoperatively, the 164 eyes had a mean IOP with medication of 18.5 mm Hg. The average mean deviation on the visual field was -6.19 dB MD, and mean cup/disc ratio was 0.59.

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Twenty-nine eyes (18%) had previously been treated with selective laser trabeculoplasty (SLT), and 8 eyes had undergone previous surgery that included placement of the Xen Gel Stent (Allergan), canaloplasty, trabeculectomy, or iridotomy. 

All of the previous interventions were performed more than 3 months prior to the combination cataract/MIGS procedure.

Of the 164 implanted eyes, 157 had 24 months of follow-up; 129, 85, and 61 eyes were seen at months 26, 48, and 60 months, respectively. 

Mean IOP decreased to 16.0 mm Hg at 1 month after surgery, 15.5 mm Hg at month 6, and stabilized at that level (±0.5 mm Hg) for the remaining follow-up duration.

At baseline, patients were taking a mean of 1.47 medications to lower IOP (range 0-4). Throughout follow-up, no patients were taking more than 2 medications, and the mean of medications used daily ranged from 0.17 to 0.23 without any evidence of an increase over time.

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Highlighting the safety of the combination procedure, Klabe reported that there were very few complications in the series. The majority of the complications were minor and related to the MIGS procedure. 

They included hyphema in 11 eyes (6.7%), persistent hypotony (IOP < 10 mm Hg for more than 1 month) in 2 eyes (1.2%), and iris incarceration in 2 eyes (1.2%). In addition, there were 7 cases (4.3%) of stent occlusion.

“The cases of occlusion were observed later than 3 months after surgery and were related to implantation that was too deep,” Klabe said. “It is very important to hold the injector in place without pushing it forward during implantation. However, the introduction of the iStent [inject] with a wider flange solved the risk of overimplantation.”

Data regarding the need for further glaucoma surgery provided further evidence of the efficacy of the combination surgery.

Eliminating the potential land mines in glaucoma surgery

Over the 5 years of follow-up, only 7 eyes (4.3%) underwent a second procedure, which included placement of the Xen Gel Stent in 3 eyes, implantation of the Preserflo MicroShunt (Santen) in 2 eyes, SLT in 1 eye, and cyclophotocoagulation in 1 eye.



The 2 microstents are preloaded in a specially designed applicator in a procedure that has a short learning curve but requires minimal additional settings and instruments, according to Klabe.

“When combined with phacoemulsification, the glaucoma portion of the procedure can be done either prior to or after the cataract surgery, according to the surgeon’s preference,” he said.

Surgical decision-making in the era of MIGS

Klabe explained that he prefers to perform the stent implantation at the end of the surgery, noting that the deep anterior chamber offers excellent visibility and lowers the risk of iris damage.

“On the other hand, the main incision in my cases is only 2.2 mm and prevents the loss of [the] ophthalmic viscosurgical device and flattening of the anterior chamber,” he said. “Use of a Vold Gonioprism with retention ring may be helpful because of the low pressure on the cornea that guarantees good visibility.” 


Klabe is a consultant/adviser to, study investigator for, and recipient of travel stipends from Glaukos and other companies that market devices for MIGS.

Retrospective review highlights the sustained efficacy of combination procedure.

Cheryl Guttman Krader, BS, Pharm

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Physician shines spotlight on mass distribution of azithromycin for trachoma control