The first-line treatment for multiple sclerosis (MS), fingolimod 0.5 mg (Gilenya, Novartis), reduces both the number of relapses and disease progression in patients with relapsing-remitting MS and may reduce the incidence of uveitis, which is higher in this patient population compared with the general population. 

However, the downside is that the drug can cause fingolimod-associated macular edema (FAME), and patients require close observation.

The drug works by blocking movement of central memory T-cells from the lymph nodes to the blood stream and has been shown to have a favorable effect on murine models of experimental autoimmune uveitis, according to Bradley Smith, MD, and Scott Sonne, who discussed the topic during a presentation at the American Academy of Ophthalmology’s virtual 2020 annual meeting.

Dr. Smith is a physician partner at The Retina Institute in St. Louis and an instructor in Clinical Ophthalmology & Visual Sciences at the Washington University School of Medicine in St. Louis, MO. Sonne is from the St. Louis University School of Medicine in St. Louis.

The investigators conducted a retrospective analysis

 to determine the incidence of uveitis and macular edema in patients with MS who were treated with fingolimod 0.5 mg. The study patients were identified in the electronic health record at The Retina Institute.


A total of 188 patients were included in the study; they had been followed for from 1 to 104 months (mean, 60.9) after treatment with fingolimod.

The authors reported that no patient had or developed uveitis. Acute macular neuroretinopathy developed in 1 patient. Twenty-six (13.83%) patients had a history of optic neuritis and 7 (3.7%) had a recurrence during the study. Fingolimod was discontinued in 3 patients after 57, 43, and 13 months for nonophthalmic reasons.

FAME developed in 3 (1.6%) patients, none of whom had intraocular inflammation or another identifiable cause of the ME.

The authors also reported good visual acuity (VA) results in most patients, i.e., 20/40 or better in 93% of eyes; 5% had a VA ranging from 20/50 to 20/200, and 2% had a VA below 20/200.

“The VA in 2 eyes was worse than 20/400 as a result of optic neuritis. Additional causes of visual loss in the patients with worse than 20/100 were optic neuritis, ischemic optic neuropathy, ruptured globe, keratoconus, macular hole, and amblyopia,” they commented.

It is recognized that uveitis occurs more frequently in patients with MS and develops in from 3.6 to 9 years on average. By contrast, uveitis did not develop in this patient cohort after a mean follow-up exceeding 5 years.

According to the investigators, fingolimod was well tolerated.

“Our retrospective review suggests possible efficacy against the development of uveitis in an at-risk population that is consistent with fingolimod’s anti-inflammatory effect in animal models,” they said. 

However, the investigators concluded that more work will need to be done to confirm or deny this possibility.

“Although there was a higher incidence of FAME, all patients were treated successfully with topical therapy,” they said.


Dr. Smith has no financial interest in this subject matter.

1. Sonne SJ, Smith BT. Incidence of uveitis and macular edema among patients taking fingolimod 0.5 mg for multiple sclerosis. 

 2020 Sep 21;10(1):24; https://doi.org/10.1186/s12348-020-00215-1

Articles

Bradley Smith, MD, presents at AAO 2020 on how fingolimod 0.5 mg, a first-line treatment for multiple sclerosis, may reduce both the number of relapses and disease progression in patients with relapsing-remitting MS as well as the incidence of uveitis.

AAO: Fingolimod for MS offers disease control with no development of uveitis

Charles Bonnet syndrome (CBS) is characterised by visual hallucinations in individuals who are experiencing sight loss, with no psychiatric or cognitive basis. It was first described by Swiss philosopher Charles Bonnet in 1760, whose father was troubled by these symptoms after losing his sight.

Since then it has been mostly associated with the elderly, reflecting the mean age at which common underlying conditions, such as age-related macular degeneration, diabetic retinopathy and glaucoma, occur. It has an estimated prevalence of between 11–15% of adults accompanying any form of visual impairment. However, CBS can affect individuals of any age including children, and so having an awareness will improve detection and management of symptoms.

, we identified the largest series of 13 paediatric and young adult patients from electronic patient records over a 9-year period presenting to Moorfields Eye Hospital NHS Foundation Trust in London.

 Nearly 70% were male and the median age of onset was 11 (range 9–19) years old. Most patients had significantly reduced vision at onset, with best corrected visual acuity in the better eye being 0.81 LogMAR.

It may be possible to identify the at-risk cohort, as over 60% of patients were diagnosed with an inherited retinal disease (IRD). The most prevalent cause was Stargardt disease, which is the commonest childhood macular dystrophy. Other IRDs included Usher syndrome, Batten disease and Leber congenital amaurosis.

The remaining cases were affected with congenital eye disorders, including microphthalmia and ocular coloboma, or optic nerve pathology, such as bilateral optic atrophy secondary to spontaneous intracranial haemorrhage and a hereditary optic neuropathy. There was no clear correlation between visual dysfunction (e.g., loss of central vision versus peripheral visual field loss) and CBS, hence there should be no visual acuity or functionality threshold before physicians advise or enquire about CBS symptoms.

In the published case series, clinicians-in-training were the most frequent reporting healthcare professional, followed by optometrists, then consultant-grade. Children presenting with these developmental eye disorders are likely to be managed in tertiary referral centres within specialist services, and so we need to raise professional awareness amongst ophthalmologists and allied health care professionals, including orthoptists and optometrists (especially those specialising in low vision services) of the importance of informing families about CBS as well as encourage them to enquire about symptoms.

The visual hallucinations may not necessarily manifest in the initial stages of the disease but could trigger during the active sight loss phase. Hence, forewarning patients and families with information on CBS and hallucinatory experiences, including strategies for symptom management and sources of emotional support, may reduce the psychological impact if they do develop symptoms.

The cause of these visual hallucinations is still unknown; current thinking suggests that reduced visual input due to systemic or retinal dysfunction results in spontaneous hyperexcitability and disinhibition of the visual cortex, resulting in these experiences. The spectrum of visual hallucinations ranges from simple geometric patterns and landscape scenes to more complex images with small figures or people, objects and distorted faces. The majority of children reported simple hallucinations, but two had more complex hallucinations and in a significant proportion it affected their personal lives including education, diet and sleep.

It has previously been suggested that children believe their hallucinations to be real, hence they are more susceptible to maladaptive responses such as fear and distress. This contrasts with adults, who do not always feel troubled by their hallucinations, as most individuals are aware that the images they are seeing are not real. Further research on the psychological impact of CBS in paediatric and adolescent patients is warranted.

The clinical management of CBS involves the implementation of simple yet effective psychological coping strategies, including brain shunting exercises such as frequent blinking or rapid eye movements, attempting to touch or brush away hallucinations, moving to brightly lit areas and increasing social interactions

. Families should be linked to local family support services and any patient can access support groups such as Esme’s Umbrella (www.charlesbonnetsyndrome.uk).

We know there is consistent under-reporting of symptoms and difficulty with case ascertainment; this is arguably a shortcoming of current paediatric ophthalmology services. The whole multidisciplinary team must raise awareness of CBS with children, and actively ask patients or families about symptoms.

We are now conducting a prospective study to try to ascertain the prevalence of CBS in the paediatric population across the UK with the support of the British and Irish Orthoptic Society and the Thomas Pocklington Trust. Further research into CBS is required in order to gain a deeper understanding of the cause and how best to manage symptoms. Natural history studies into the longevity of visual hallucinations, especially in childhood, will also help when advising parents of the future prognosis.

Mariya Moosajee, MBBS, BSc, PhD, FRCOphth

Prof. Moosajee is professor of molecular ophthalmology at UCL Institute of Ophthalmology, group leader of ocular genomics and therapeutics at The Francis Crick Institute and consultant ophthalmologist specialising in genetic eye disease at Moorfields Eye Hospital and Great Ormond Street Hospital for Children, London, United Kingdom. She has no financial disclosures related to the content of this article.

Jones L, Moosajee M. Visual hallucinations and sight loss in children and young adults: a retrospective case series of Charles Bonnet syndrome. 

. 15 Sep 2020. DOI: 10.1136/bjophthalmol-2020-317237.

Best J, Liu PY, Ffytche D, Potts J, Moosajee M. Think sight loss, think Charles Bonnet syndrome. 

 20 Dec 2019. DOI: 10.1177/2515841419895909

A case series of 13 young patients with Charles Bonnet syndrome, which is characterised by visual hallucinations in individuals who are experiencing sight loss, showed that the patients all had inherited retinal diseases or congenital eye disorders but there was no link with visual dysfunction.

The importance of recognising Charles Bonnet syndrome in children


Kristen Brotherson, vice president, US surgical marketing for Alcon, discusses some of the recent advances in cataract surgery-related technologies, including a new advanced lens for patients with presbyopia (AcrySof IQ Vivity IOL).

Videos

Kristen Brotherson, vice president, US surgical marketing for Alcon, discusses some of the recent advances in cataract surgery-related technologies, including a new advanced lens for patients with presbyopia (AcrySof IQ Vivity IOL).

AAO: Alcon showcases advanced IOL technology for presbyopia


Rick Eiswirth, president and CEO of Alimera Sciences, provides an update on the company’s clinical trial that aims to evaluate its fluocinolone acetonide intravitreal implant 0.19 mg (Iluvien) as a baseline therapy for diabetic macular edema.

AAO: Alimera highlights NEW DAY Study for sustained-release intravitreal implant


Rudy Nuijts of the University Eye Clinic Maastricht, the Netherlands, discusses the highlights of his AAO 2020 presentation on a combination treatment regimen for lowering the incidence of cystoid macular oedema following category surgery.

AAO: Preventing cystoid macular oedema after cataract surgery


Cynthia Matossian, MD, FACES, ABES, of Matossian Eye Associates, presents the highlights of a poster on outcomes with dexamethasone intraocular suspension 9% and concomitant postoperative anti-inflammatory medications. 

The study examined early experiences among cataract surgeons with the use of the injectabcle ophthalmic anti-inflammatory medications.

Cynthia Matossian, MD, FACS, ABES presents the highlights of a poster on outcomes with dexamethasone intraocular suspension 9% and concomitant postoperative anti-inflammatory medications.

Cynthia Matossian, MD, FACS, ABES, presents the highlights of a poster on outcomes with dexamethasone intraocular suspension 9% and concomitant postoperative anti-inflammatory medications.

AAO: Medication could reduce burden of steroid drops for patients

Autologous retinal transplant (ART) for macular holes, a relatively new procedure, is providing anatomic hole closure in the vast majority of cases of large macular holes as well as increases in visual acuity (VA). 

In addition to the macular hole closure, the keys to better final outcomes were ellipsoidal band reconstitution and alignment of the neurosensory layers.

In this procedure, which was developed by Tamer Mahmoud, MD, PhD, an autologous neurosensory retinal free flap is harvested and moved over the hole to cover the hole gap and connect to surrounding macular tissue for large holes in which the mean minimal linear diameter exceeded 800 μm in the study.

, a professor of ophthalmology at Oakland University William Beaumont School of Medicine, and Associated Retinal Consultants in Royal Oak, MI

, presented the information at the American Academy of Ophthalmology’s virtual 2020 annual meeting on behalf of the ART Team Study. 


In a multicenter, international, case series in which 33 surgeons participated, 130 eyes of 130 patients (women, 58%; mean age, 63±6.3 years) underwent ART to treat their macular holes. All patients underwent a pars plana vitrectomy and ART during the study from January 2017 through December 2019. 

Dr. Mahmoud and his colleagues sought to determine the anatomic and functional outcomes of ART for the surgical repair of primary and refractory macular holes and macular hole retinal detachment (MHRD). This study is in press in 

Of the 130 patients, 35 (27%) had primary macular holes and 76 (58%) had refractory macular holes. Among the patients, 19 (15%) also had a MHRD, that was recurrent in 13 cases, and 12 of the 19 patients had a recurrent MHRD and had undergone previous internal limiting membrane (ILM) peeling. The mean number of surgeries that the patients had undergone previously was 1.6±0.2 (ILM peeling and flaps).

Dr. Mahmoud recounted that the patients’ mean preoperative axial length was 24.6 ± 3.2 mm, the mean maximal hole diameter 1,470 ± 160 μm, and the mean minimal hole diameter 840 ± 94 μm. The preoperative logarithm of the minimum angle of resolution best-corrected VA (logMAR BCVA) was 1.37 ± 0.12 (~20/500).

The graft type was a 90% neurosensory retina without the choroid that was harvested in 45% of cases superiorly, 17% inferonasally, 11% superotemporally, 8% each superonasally, and inferiorly, 7% temporally, and 4% inferotemporally. 

In 84% of cases, the harvest site was posterior to the equator and in 16% anterior to the equator. Most grafts (70%) ranged in size from 0 to 1 disc diameter (DD), 29% from 1 to 2 DD, and 1% 2 to 3 DD.

When the grafts were positioned in the eyes, 81% were placed preretinally and the remainder subretinally. The mean follow-up time was 8.6 ± 0.8 months.

The reconstitution of the external limiting membrane and the ellipsoidal zone is important to the success of the procedure.

“In this study, we introduced the term “ANL” or alignment of the neurosensory layers,” Dr. Mahmoud said. “When the graft is first moved to the hole area, vertical lines are seen on optical coherence tomography [OCT] between the graft and surrounding macular tissue.”

Dr. Mahmoud noted that within the first few weeks, those lines gradually fade and details of graft layers can be detected and those align with similar layers in the surrounding host macular tissue, plexiform to plexiform, nuclear to nuclear, etc.

“We feel this is remarkable as the macular tissue recognizes the retinal tissue and may try to connect to respective layers creating that integration of the retinal transplant, which reflects on better visual outcomes,” he said.

The final postoperative logMAR BCVA improved significantly (p<0.001) to 1.05 ± 0.09 (~20/225), with 29% of patients gaining more than 5 lines of vision and 43% gaining 3 lines of vision.


Fifteen (12%) patients had a final VA of 20/50 or better; among these, a third had a primary macular hole and two-thirds a refractory macular hole. 

The mean preoperative BCVA in this subgroup was 0.848 ± 0.219 (~20/125) and the mean final BCVA was 0.308±0.079 (~20/40), a difference that reached significance (p<0.001). 

Two-thirds gained more than 3 lines and 40% more than 5 lines; all of these holes closed. In addition, two-thirds had a complete ellipsoidal zone.

According to Dr. Mahmoud, the global study reflects the initial experience worldwide, with most surgeons sharing their initial experiences.

“With better understanding of prognostic factors and refinement of surgical techniques developed throughout this collaboration, anatomic closure can be achieved in most large macular holes, which would reflect on better visual outcomes,” he said. “This also paves the way to further research the role of peripheral retina into acquiring macular function and its potential in many macular diseases.”

The postoperative complications included 5 cases of retinal detachment, 5 cases of ART graft dislocation, and 2 cases of subretinal perfluoro-N-octane. Endophthalmitis was suspected in 1 case. There were 5 cases of ART graft dislocation (3.9%).

Dr. Mahmoud enumerated the main study points, including that the preoperative diagnosis (p = 0.026) and preoperative VA were associated significantly (p < 0.001) with the postoperative VA, and that the macular hole closure (p < 0.001), reconstitution of the ellipsoid zone band (p=0.02), and alignment of neurosensory layers (p = 0.01) on OCT were associated with better final VA.

The results showed a high rate of closure (89%) of the macular holes and 95% in MHRD. The gains in VA were substantial, in that 29% of cases had at least a 5-line gain in visual acuity and 43% had at least a 3-line gain in visual acuity.

“The higher final levels of VA were associated significantly with macular hole closure (p < 0.001), reconstitution of the ellipsoid zone band (p = 0.02), and alignment of the neurosensory layers (p = 0.01) on OCT images,” Dr. Mahmoud concluded.

Dr. Mahmoud has no financial interest in this subject matter.


1. Moysidis SN, Koulisis N, Adrean SD, et al. Autologous retinal transplantation for primary and refractory macular holes, and macular hole retinal detachments: The Global Consortium. 

 2020; Published online: October 9, 2020.

Tamer Mahmoud, MD, PhD, discusses autologous retinal transplant (ART) for macular holes, a procedure he developed, which is providing anatomic hole closure in the vast majority of cases as well as increases in visual acuity. 

AAO: Autologous retinal transplant for larger macular holes gaining traction


2020 has been a strange year for healthcare and medicine, and many now look to 2021 with hope for better times ahead. As we leave the year behind, five members of the 

Editorial Advisory Board share their perspectives and predictions on new developments and challenges that will affect ophthalmology in the new year. Themes in the wake of the COVID-19 pandemic include cost savings and patient selection, alongside an interest in technology and digital applications, while concerns about refractive disorders, cataract surgery, glaucoma and retinal disease remain important.

 is professor and chair of the Department of Ophthalmology, Klinikum Karlsruhe, Karlsruhe, Germany.

 is professor of ophthalmology and chairman of the Quinze-Vingts National Ophthalmology Hospital, Paris, France.

is clinical professor in ophthalmology and optometry and was formerly based at the University Eye Clinic of the Medical University of Graz, Austria.

is professor of clinical ophthalmology at Queen’s University Belfast, Belfast, Northern Ireland.

is a consultant ophthalmic surgeon at St Thomas’ Hospital, London, UK, and is honorary consultant to the Royal Hospital Chelsea (the Chelsea Pensioners) and King Edward VII’s Hospital for Officers, London.

Small-incision lenticule extraction (SMILE) is increasingly being preferred over conventional flap-based procedures for the treatment of refractive errors. The procedure involves different phases, such as docking, femtosecond laser application, lenticule dissection from the surrounding stroma and extraction. Various techniques have been described to simplify the process of lenticule extraction and minimise complications.

Many authors have nicely demonstrated that SMILE is comparable to femtosecond LASIK (FS-LASIK) in terms of safety, efficacy and predictability, showing advantages of better ocular surface stability and biomechanical strength compared with FS-LASIK. Nevertheless, I suggest that proper patient selection is crucial to achieve the best visual outcome. With increasing surgical experience within the next few years, a standard technique is expected to evolve that may be performed in all types of cases, with optimal outcomes and minimal adverse effects, making SMILE a leading procedure in refractive surgery worldwide.

Glasses for presbyopia should be offered at a reasonable price to all people, including in developing countries. Progressive lenses are the optimum choice for people who need them due to refractive problems in their distance vision.

Another refractive issue is high myopia: to try to prevent this from occurring, it is important to recognise myopic axial length early and treat with atropine eye drops, as well as ensuring children go outside and so are exposed to sunlight for at least 2 hours a day. In addition, if possible, special contact lenses can be used, for example, MiSight (Cooper Vision), MyoVision (Zeiss), Myopilux (Essilor) or MiyoSmart (Hoya); or glasses with a special design such as the Stellest lens (Essilor).

Another suggestion is adapting computer desktops so that bright text is read on a dark background. It is also important to disseminate information on the fact high myopia at a young age may lead to severe sight-threatening diseases of the eye, such as retinal detachment, myopic maculopathy or glaucoma.

Post COVID-19, the cost pressures on cataract surgery will be relentless. Immediate bilateral sequential cataract surgery (IBSCS) will become the treatment of choice. Studies show no difference in refractive outcome or complications compared with sequential surgery and there are advantages for the patient, the hospital and the financial provider. Careful patient selection, high-quality biometry and surgery, and operating theatre logistics are the keys to success, and studies show that IBSCS is appropriate for more than 70% of patients.

Monofocal IOLs with enhanced depth of focus such as Vivity (Alcon), Tecnis Eyhance (Johnson & Johnson Vision) and ME4 (Santen) will displace standard monofocal IOLs because they offer patients more spectacle independence with negligible dysphotopsia. The Carlevale IOL will become the implant of choice for sulcus fixation in the absence of capsular support. And, building on femtosecond laser, eye-tracking technology and three-dimensional imaging, we will start to see the beginnings of robotic cataract surgery.

 High-quality cataract surgery in developing countries should be a focus: doctors should be supplied with good microscopes, modern biometry machines, proper surgical equipment and autoclaves, and IOLs in many dioptres (spherical and cylindrical). They should also be trained in phacoemulsification and small-incision extra-capsular cataract surgery techniques. These should be offered to the patients at a reasonable price and patients should be transported free-of-charge to surgical centres by social services.

Glaucoma therapy represents a tough challenge for general ophthalmologists and glaucoma experts alike. Despite the wide armamentarium of medical therapies currently available, it can be an arduous task to obtain the optimal target intraocular pressure (IOP) for each patient.

In recent years, I have implemented laser treatment in the management of glaucomatous patients, which has proved a safe alternative to other treatment modalities such as topical therapy. In addition, it has a favourable side effect profile.

Different types of laser treatment have been proposed. Among them, selective laser trabeculoplasty and laser transscleral cyclophotocoagulation have been shown to reduce IOP by increasing aqueous outflow and decreasing aqueous production, respectively.

In addition, a new subthreshold laser technique, micropulse transscleral cyclophotocoagulation (mTS-CPC), has been developed as a potential alternative to traditional laser procedures. The micropulse modality, which is characterised by off cycles, allows thermal dissipation and thus leads to less collateral damage such as tissue scarring. mTS-CPC deserves consideration as a first line choice of procedure for treating patients with primary open-angle glaucoma because of its outstanding effectiveness and limited side effects profile.

Fifty percent of glaucoma patients are undiagnosed because there is a lack of education compared with diseases such as diabetes, hypertension, high cholesterol and several cancers. Also, there are fewer ‘goodies’ to incentivise preventative check-ups, such as discounts to insurance costs.

Education should start with regular spots or movies on TV and/or on smartphones. Lost retinal nerve fibres cannot be brought back again: it is impossible to buy, borrow or lease them, even for millionaires.

Unnecessary therapies should be avoided in eyes without any glaucomatous changes. IOP that is higher than statistically normal does not point only to glaucoma and is very rarely an indication for therapy. Establishment of an individual risk profile will save money and will avoid the possible side effects of therapy.

Three-dimensionalvisualisation during vitreoretinal surgery is critical to achieve the best anatomical and functional outcomes, given the delicate and microscopic features of retinal structures. Many studies have shown that 3D imaging technology in vitreoretinal surgery is associated with improved ergonomics and enhanced surgical team communication and education, as well as with reduced retinal phototoxicity and increased depth of surgical field. In particular, physician questionnaire survey scores demonstrated a better depth of field at high magnification for the digital 3D system.

The next step, already reached, is represented by the integration of optical coherence tomography (OCT) into the digital visualisation system, which allows intraoperative display of OCT images on a 4K screen, facilitating the identification of subtle retinal alterations. In addition, the digital platform enables the simultaneous view of OCT and the surgical field. In my opinion, a step forward is necessary in order to allow a ‘real’ simultaneity between the retinal image, as seen by the surgeon under the microscope, and the corresponding OCT image.

Digital progress permeates all aspects of our lives and is becoming increasingly present in surgical departments such as the ophthalmologic operating room. It is only a matter of time before improved 3D visualisation systems are regularly used in most surgical settings.

 Telemedicine and tele-ophthalmology have played prominent roles in ophthalmology for a while, but never more so than during the COVID-19 pandemic. During this time, healthcare providers and patients learnt to use software that enabled online communication and telemedicine triage. This resulted in many patients not having to attend face-to-face consultations.

In 2021, the challenge will be to test the safety of this approach and address the ‘missed’ cases when they eventually present. We must learn from these and then make the telemedicine approach even more widely available for those aspects of ophthalmology where it proves to be safe and sustainable.

Home monitoring for medical retinal diseases, such as age-related macular degeneration, has been steadily growing, but our understanding of how to roll this out safely is limited. In addition, many of the necessary devices are not widely available and there is not enough information about where they fit safely and sustainably into the current clinical pathways.

There is also not enough data on how the consultations resulting from these examinations will be managed, and in some countries, reimbursed. The challenge in the next year will be to incorporate more home-monitoring devices and techniques into clinical pathways in order to minimise unnecessary hospital visits while maintaining treatment opportunities for those who do need to attend.

Retinal disease, diabetic eye disease and gene therapy

For a long time, there was no cure for people affected by inherited retinal diseases. However, in recent years, genome sequencing techniques have allowed us to discover new genes and pathogenetic mechanisms underlying such diseases. Thus, alongside diagnostic and prognostic tools, new therapeutic perspectives are emerging.

In particular, I would like to highlight the development of a new revolutionary gene-editing technique, the CRISP-Cas9 system. It has provided a fresh approach to gene therapy in every medical field, including ophthalmology. Trials in humans have already been conducted with very promising results for both X-linked and autosomal dominant forms of retinitis pigmentosa as well as Leber hereditary optic neuropathy, for which the first gene therapy product voretigene neparvovec (Luxturna) was recently approved.

The main challenge for the future will be the identification of optimal, less-invasive gene delivery systems. In this respect, I would like to stress the importance of an up-and-coming technique: sonoporation. In my opinion, this method might change the paradigm of inherited retinal disease management.

The sonoporation technique uses microbubbles of ultrasound contrast agents containing the relevant gene-editing system with the application of ultrasound to the region of interest in order to deliver gene therapy to specific organs. Hopefully we will soon be able to tell our patients suffering from inherited retinal diseases that we will be able to help them.

Diabetes is an established risk factor for poor outcomes in patients with COVID-19; therefore, during the pandemic many patients have been asked to shield or self-isolate for extended periods of time. At the same time, many have required ophthalmic examination and treatment, and none of these can be completed using telemedicine.

Face-to-face consultations and treatment are time-consuming, increasing the risk of infection. Those patients requiring treatment were subjected to significant delays in accessing what they needed and some even progressed to sight loss. In 2021, all newly diagnosed diabetes patients in addition to those with delayed treatment will need to be seen and treated.

We must develop a better recognition of the severity of dry-eye disease (DED): it is rarely sight-threatening but, besides having a major impact on quality of life, it also impairs quality of vision, resulting in unstable vision, ocular fatigue and difficulties in concentration and working on a computer. Efforts must therefore be made to help patients who are deeply and continuously suffering.

We also need a greater appreciation of the discrepancy between signs and symptoms of DED. Patients often complain of very severe symptoms but the clinician may lack the tools to understand the reasons for them. On the other hand, others experience such severe corneal damage that they do not suffer any more and develop neurotrophic keratopathies that link corneal defects to dry eye, acting together as a vicious cycle. Such cases may be due to chronic inflammation and lymphocyte activation, which is often difficult to identify clinically.

Confocal microscopy assessment of the cornea and new-generation OCT with higher resolution may be helpful but are not always available for clinicians. Other new technologies, such as meibography, tear film interferometry, aberrometry and topography, are becoming progressively more available but remain mostly limited to research centres.

Inflammation has been recognised as a major underlying mechanism of DED but we are unable at present to precisely identify inflammation levels, its mechanisms and severity. There are several types of inflammation present in the disease, which are mediated by Th1, Th2 or Th17 lymphocytes, B-cell autoantibodies or innate immunity, and complex interactions exist between the inflammatory cascades, mediators and cellular actors. Biomarkers, especially in point-of-care settings, would bring valuable information to target precisely the mechanisms of DED, in order to help damaged ocular surface tissues to recover and relieve patients of their disabling symptoms.

Neuropathic pain has emerged in recent years as an explanation for the significant symptoms that patients with mild or no visible clinical signs exhibit, or in cases of persistent symptoms despite improvement of the initial lesions, namely, corneal damage. The brain becomes chronically stimulated in a pain mode, which subsequently affects patients’ mood and leaves them at risk of depression. The chronic pain is very difficult to alleviate and may require specific pain-relieving strategies.

The pain may be explained by repeated or sustained stimulation of cold receptors of the corneal nerves. Confocal microscopy of the corneal nerves may sometimes recognise signs of chronic nerve activation, such as neuromas and inflammatory infiltrates. Targeting cold and/or noxious receptors of corneal nerves will certainly be another promising challenge of the next few years.

Customised or tailored therapies based on disease mechanisms will continue to be developed: most DED therapies remain based on corneal lubrication and tear substitution, which is not sufficient in severe cases. New immunomodulating strategies have been developed and have changed the paradigm from treating the consequence, i.e., dry eye, to targeting the causes(s), namely inflammation. Other agents could be developed to block more specific mechanisms, such as tumour necrosis factor, interferon or microbiota-associated cascades of mediators.

The management of severe ocular surface diseases such as corneal ulcers and chemical injuries has changed dramatically over recent years. Amniotic membrane transplantation (AMT) is currently playing a fundamental role in the treatment of these disease entities.

This surgical procedure has proven to be a safe and effective alternative to traditional corneal transplantation, and has shown to be able to reduce intraoperative complications and improve visual acuity. The beneficial effects result from the amniotic membrane’s anti-inflammatory and anti-fibrotic properties. In addition, AMT contains growth factors that promote epithelial wound healing on the ocular surface.

In our clinic, we are improving the use of AMT for corneal and conjunctival reconstruction in many clinical situations, including acute chemical burns, persisting corneal ulceration of varying aetiologies and in cases of conjunctival scarring, such as for conjunctival neoplasia and pterygium surgery. Thus, AMT can be considered a major breakthrough in reconstructive eye surgery, providing us with the possibility of treating chronic surface diseases with a high safety and efficacy profile, and thereby minimising surgical time and intraoperative risks.

‘Gadgets’ are worth mentioning as we look to 2021: ophthalmologists should remain alert in avoiding all surgeries that can be considered strange and unnecessary, such as changing the colour of the iris by implants. This type of surgery amounts to complete nonsense and destroys the eyes. Even if people are prepared to pay a large amount of money, all seriously thinking and acting doctors should say “no” to conducting such surgeries.

 Working relationships between patients and healthcare professionals and amongst clinical teams changed beyond recognition in 2020: keeping a distance away from each other, wearing masks and not seeing our patients as frequently as planned had profound effects on how we communicate. Adding these aspects to the fact that many medical retina patients are either elderly, have significant comorbidities or have visual and/or hearing loss (of a combination of all of the above), giving information and displaying empathy using well-understood facial expressions has to be re-evaluated.

In 2021, the challenge will be to re-establish relationships, making sure that patient information is up to date and is understandable by all, even to those who do not use online resources, and making sure nobody is left behind without access to treatment. Research is crucial for treatment provision: it is well established that those ophthalmology units that have an active research profile have better outcomes in treating patients in their clinics.

The rigorous thinking process required for conducting good-quality research and the necessity of keeping up to date with the relevant topics have a long-lasting impact on how we treat our non-research clinical patients as well. Many clinicians also play a role in basic science and/or translational research and these have long-term effects on treatments offered in the future.

The challenge at our clinic will be to rebuild research portfolios and programmes that have been stopped because of the pandemic, refocus our research intentions on those fields that emerged as important, and re-evaluate how we involve our patients in framing our questions and research priorities.


Prof. Augustin declares that he recieves advisor and speakers honoraria with Allergan and Alimera.


Prof. Baudouin declares interests with Aerie, Alcon, Allergan, Horus Pharma, Santen and Thea.


Prof. Faschinger declares no financial interests.


E:  T.Peto@qub.ac.uk
Prof. Peto declares no financial interests.


E:  profspalton@gmail.com
Prof. Spalton is a consultant to Optical Express, AnewOptic Inc., AVS/Santen and Keensight.

In this roundtable, members of the Ophthalmology Times Europe® Editorial Advisory Board consider the top challenges and opportunities that they anticipate will affect ophthalmology in Europe in 2021.

Ophthalmic challenges in 2021: What to expect in the coming year



Robert Weinstock, MD, director of Cataract & Refractive Surgery, The Eye Institute of West Florida; the Weinstock Laser Eye Center, presents real-world data from a retrospective multicenter study focusing on the efficacy of dexamethasone intraocular suspension 9% delivered at the time of cataract surgery.

Weinstock notes that research shows the injections can decrease inflammation and control IOP.

Robert Weinstock, MD, presents data from a retrospective multicenter study focusing on the efficacy of dexamethasone intraocular suspension 9% delivered at the time of cataract surgery. 


AAO: Study outlines use of injectable intraocular steroid over drops

Physicians at Kaiser Permanente have been using a prophylactic drop-free drug regimen before cataract surgery for more than a decade. 

Their regimen is so streamlined that the only drop that patients receive in anticipation of cataract surgery is a supplemental dilation drop instilled preoperatively while they are still in the holding area, according to Neal H. Shorstein, MD, who discussed the topic at the American Academy of Ophthalmology’s virtual 2020 annual meeting.

Dr. Shorstein is an ophthalmologist, researcher and associate chief of quality at Kaiser Permanente Medical Center in Walnut Creek, CA.

This more efficient approach seems highly beneficial for patients because drop instillation is associated with a few risks, i.e., prescription error, failure to pick up the prescription, failure to adhere to the instillation instructions, and stopping the drops prematurely. 

If only the correct instillation is considered, 93% of drop-naive patients have been reported to instill drops incorrectly. In addition, the bottle tip can become contaminated and it can cause microtrauma. 

The resistance of bacteria to topical antibiotics is another issue, such that instillation periods that are too short or too long or repeated over time can result in bacterial resistance. Finally, and not to be overlooked, the drugs can be expensive.


The regimen begins with an injection of LidoPhen 1%/1.5% (cyclopentolate/tropicamide, VNH Pharmaceuticals Pvt, Ltd.) at the beginning of the surgery.

The surgery ends with an injection of at least 0.5 ml of intracameral moxifloxacin 0.1%. 

However, 0.1 ml of cefuroxime 1% can be substituted in place of the moxifloxacin. Moxifloxacin also can be used for stromal hydration because recent data have indicated that the antibiotics remain in the wound for about 24 hours.

Finally, at least 4 mg of subconjunctival triamcinolone acetonide is injected at least 5 mm inferior to the inferior limbus. No perioperative topical nonsteroidal anti-inflammatory drug (NSAID) or steroid is used, Dr. Shorstein explained.


The use of moxifloxacin in the manner described for stromal hydration and in an intracameral injection has been associated with low endophthalmitis infection rates. 

This was supported by a meta-analysis that concluded that there was no supporting evidence that any postoperative use of topical antibiotics lowered the risk of endophthalmitis. 

Another study found no difference in the endophthalmitis rates with or without the use of short-term topical antibiotics in conjunction with a regimen of intracameral antibiotics, according to Dr. Shorstein.

A look at the studies that evaluated triamcinolone injections during cataract surgery showed that similar or better control of inflammation was achieved with subconjunctival injection compared with topical steroid instillation or with a steroid plus an NSAID in the 2017 PREMED Study. 

In the latter, the inflammation was well controlled in patients with diabetes who did not develop cystoid macular edema, but the intraocular pressure (IOP) was higher because of a higher subconjunctivally injected steroid dose, he pointed out.

That result leads to consideration of the importance of dose and injection site.

“Location is everything,” Dr. Shorstein said. “Injecting steroid closer to the limbus produces a higher concentration of the steroid in the aqueous and a higher mean IOP at 3 months compared with the same dose injected more posteriorly resulting in a lower aqueous concentration and a lower mean IOP.”

There is a tradeoff when injecting the drug more anteriorly. Pain and iritis are addressed but it carries the increased risk of higher IOP. Injecting more posteriorly should be more beneficial to the macula with less chance of IOP spikes ,but perhaps at the expense of enhanced pain and iritis control.

Initially, Dr. Shorstein reported, the drop-free regimen included the concentrated form of triamcinolone that resulted in some IOP spikes; with the same dose but injecting a greater volume (0.4 mL) of the dilute form of drug (10 mg/mL), fewer IOP spikes occurred and the physicians adhere to this practice.

“The most common problem associated with steroid injections is conjunctival hemorrhage that results from nicking a blood vessel during the injection,” he said. “This can be minimized by visualizing the needle tip and avoiding large vessels.”

Rarely, self-limited late hemorrhages months after the injections have been observed.

Drug reflux is another problem that can be avoided by tunneling the needle 2 to 4 mm under the conjunctiva and injecting slowly.

Dr. Shorstein also advises physicians to educate patients about the presence of the depot white spot and that it generally resolves in about 1 to 2 months and that, while IOP spikes occur infrequently, patients should have a checkup 1 month postoperatively.

Finally, when adhering to the dropless regimen, Dr. Shorstein noted the importance of instilling povidone-iodine 5% solution for 3 to 5 minutes, careful wound construction, leaving a relatively firm eye at the end of the surgery, and use of stromal hydration with an antibiotic.

Dr. Shorstein has no financial interest in this subject matter. The drugs mentioned are used off-label.

During AAO 2020, Neal H. Shorstein, MD, explains how physicians at Kaiser Permanente have a streamlined regimen using a prophylactic drop-free drug before cataract surgery for more than a decade. 

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AAO: Study outlines use of injectable intraocular steroid over drops

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