The respiratory symptoms caused by the severe acute respiratory coronavirus disease (COVID-19) that has been sweeping the world since late 2019 are well documented, given the regularity and consistency with which they occur. However, the role of the eyes and tears both as entry routes for the causative virus, SARS-CoV-2, and as sources of contagion are still the subject of debate, and relatively less is known about the ophthalmic implications of the disease.

It would appear from some recent studies that patients who experience the more severe forms of COVID-19 and present with pneumonia commonly display ocular symptoms. However, the authors of a recent Chinese study of 38 patients concluded that although a third of patients with the disease had ocular abnormalities, there was a low prevalence of the virus in tears1,2.

Nevertheless, it is possible that contact with infected eyes could be a route of transmission of SARS-CoV-2, especially given the knowledge that it can be spread via direct or indirect contact with other mucous membranes (the mouth and nose), so ophthalmologists should err on the side of caution and ensure rigorous prevention protocols are put in place.

In a literature review recently published in 

, Prof. Jorge Alió and Dr Alejandra Amesty reported that when it occurred, conjunctivitis was the most common ophthalmologic sign related to coronavirus infection1. And there are clues from previous coronavirus outbreaks as to why this should be the case: inflammation of the conjunctiva was first associated with a human coronavirus back in 2004 when children started to fall prey to the symptoms during the severe acute respiratory syndrome (SARS) crisis.

Genetically speaking, SARS-CoV-2, the virus that caused SARS, is around 70% similar to SARS-CoV and uses the same receptor (ACE2) to insert itself into human cells. This is potentially quite significant when one considers that ACE2 receptors have been found in the aqueous humour3.

But could the fact that conjunctivitis is mainly being seen in the most poorly patients mean that the presence of the virus on the surface of the eye and subsequent ocular events are down to decreased immune function? The researchers do not think so: “Both viral diseases and immune problems can lead to ocular manifestations, such as conjunctivitis, uveitis, retinitis, among others. It is difficult to determine the pathology of the ophthalmic involvement. However, since the virus has been cultured from conjunctival secretions, COVID-19 ophthalmopathy is more likely to be related to the actual virus infestation rather than the secondary immune reaction that the infection may cause.”

Any sign of conjunctivitis in the clinical setting should be considered to be a “possible coronavirus conjunctivitis, especially when accompanied by other respiratory tract problems or fever”, the authors pointed out.

Thankfully, viral conjunctivitis usually amounts to no more than an uncomfortable nuisance, so treatment strategies are typically supportive in nature. That said, it is important to try to lessen the potential viral load on the ocular surface and some of the general ophthalmic recommendations for viral conjunctivitis could also apply to COVID-19 patients.

“These include hygienic measures (frequent hand washing, especially when eye drops need to be applied or contact lenses worn; avoiding touching or rubbing the eyes; changing pillowcases, sheets) … we should be meticulous when examining patients who have tested positive for COVID-19.”

The close face-to-face proximity of ophthalmologists to their patients and frequent exposure to tears and ocular discharge, as well as regular handling of equipment such as slit lamps, tanometers and lasers, means they are perhaps at a higher risk of contracting COVID-19 than other types of healthcare professionals, the researchers said, referring to recent guidelines that have been published in an attempt to minimise the chances of infection spreading in ophthalmology clinics and hospital departments.4,5

In the guidance, ophthalmologists are advised to impose limits on the number of attending patients and to adhere to strict appointment timetables to prevent people from gathering in clinic waiting rooms. Online platforms, such as hospitals’ official websites, should be readily used, whilst simply making more telephone calls could reduce the need for patients to visit hospitals, for example, by helping them to distinguish between urgent and nonurgent ocular problems.

The guidelines go on to recommend triage systems to help to flag up patients with symptoms consistent with COVID-19 infection such as fever, and online ordering and delivery of prescribed medication, especially for chronic eye diseases such as glaucoma.

Recommendations for handling a patient’s visit include:

Reducing the number of accessible entry points to the hospital/clinic;

Screening patients for COVID-19 symptoms and contact history with confirmed or suspected within the past 14 days;

Seeing patients with eye infections in separate clinics with their own waiting areas;

Testing patients more than twice for evidence of SARS-CoV-2 RNA in the conjunctival sac and tears;

Limiting numbers of people in examination rooms;

Ensuring rooms are well ventilated and instruments used disinfected immediately after a patient’s visit; and

In addition, slit lamps should be protected by shields and direct ophthalmoscope examination could be replaced by slit light lenses, optical coherence tomography or fundus photography.

For inpatients, the suggested adaptations include preoperative infection screening and use of local rather than general anaesthesia to avoid contamination. Negative-pressure operating rooms should be used for emergency operations on any COVID-19-positive patients.

Human coronavirus is believed to be able to remain infectious on inanimate surfaces for as many as 9 days6, so disinfecting surfaces with water, detergent and commonly used disinfectants is extremely important, Prof. Alió and Dr Amesty explained. In addition, they suggested that some ocular spray disinfectants that contain hypochlorous acid (usually applied to treat blepharitis in order to reduce bacterial and viral load on the skin and eyelashes) could be used as “a measurement of prevention for the facial area where many other chemical agents cannot be applied”.

However, more studies are needed to establish a specific antiviral product that could be used to reduce the viral load on infected patients’ conjunctiva and lower the transmission rate via the eyes/tears. The authors conceded that this is no easy task when “so many doubts still remain regarding the ophthalmic implications” of the infection.

Summarising, the authors have called for “well-designed trials” to be conducted “to rule out other ocular manifestations [besides conjunctivitis] that may result from COVID-19 infection and to better elucidate the mechanisms of transmission through the eyes.”

Until more light can be shed on the ophthalmic implications of COVID-19, ophthalmologists can only remain as up-to-date as possible on emerging disease findings, whilst maintaining a cautious approach when dealing with patients before, during and after appointments.

1. Amesty MA, Alió del Barrio JL, Alió JL. COVID-19 disease and ophthalmology: An update.

https://doi.org/10.1007/s40123-020-00260-y

Wu P, Duan F, Luo C, et al. Characteristics of ocular findings of patients with coronavirus disease 2019 (COVID-19) in Hubei Province. China 

https://doi.org/10.1001/jamaophthalmol.2020.1291

Holappa M, Vapaatalo H, Vaajanen A. Many faces of renin-angiotensin system—focus on eye. 

Lai THT, Tang EWH, Chau SKY, et al. Stepping up infection control measures in ophthalmology during the novel coronavirus outbreak: an experience from Hong Kong. 

Yong Y, Ruixue T, Xu S, et al. A comprehensive Chinese experience against SARS-CoV-2 in ophthalmology. 

Kampf G, Todt D, Pfaender S, Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents

Prof. Alió is professor and chairman of ophthalmology at the Miguel Hernandez University of Elche and scientific director at Vissum in Alicante, Spain. He has no financial interests in the subject matter.

Articles

Emerging data on conjunctivitis cases in COVID-19 patients necessitate high levels of caution and a meticulous approach during the pandemic.

The ophthalmic implications of COVID-19: What we know so far 

A study found that the ICE2 procedure was more effective than iStent/phacoemulsification with no added risk. Safety was excellent in both groups.

Minimally invasive glaucoma surgery (MIGS) has changed the way we approach the management of glaucoma. MIGS offers the glaucoma surgeon safe and effective surgical options that have lowered the threshold for surgery, which was traditionally reserved for advanced or rapidly progressive disease.

The mindset of the glaucoma surgeon now has to evolve as well. Surgeons and patients should work together to take control of this blinding disease and no longer be a passenger.

This approach, often termed ‘interventional glaucoma’, requires the surgeon and patient to take an active rather than passive role in the management of glaucoma. Ocular surface disease, side effects of topical treatment and non-adherence should be addressed at every clinic visit to see whether more effective treatments can be offered.


	We are now entering the era of combination MIGS and exploring how to maximise the cumulative effects of these surgeries whilst maintaining the excellent safety profile that is its foundation.
	
	Synergistic approaches to lowering intraocular pressure (IOP) are not novel; they have been used in topical treatment for many years, such as combining beta blockers to target inflow and prostaglandins to improve outflow.

The iStent (Glaukos Corporation) reduces IOP when used alone or during cataract surgery. This ab interno stent bypasses the trabecular meshwork, improving the eye’s ability to drain aqueous into the Schlemm’s canal. The device is safe and effective for patients with mild-to-moderate open-angle glaucoma.

When implanted during cataract surgery, the implant adds to the potential IOP-lowering effect of phacoemulsification, which may reduce IOP to a small degree in open-angle disease and to a greater extent in primary angle-closure glaucoma.

 
	
	I have always been pleased with the reduction in IOP after iStent and phacoemulsification. I wondered whether adding endoscopic cyclophotocoagulation (ECP; BVI Medical) would enable me to achieve an even lower IOP postoperation. This could result in more of my patients’ glaucoma being controlled, as well as reducing the risk of them requiring filtering surgery in the future.

ECP safely and predictably decreases aqueous production through targeted ablation of the ciliary processes, thus lowering IOP.

 It is appropriate for the vast majority of patients, but it is contraindicated for underlying macular pathology such as macular oedema or a history of uveitis.

We recently completed a study that has been published in the 

 comparing the outcomes for patients undergoing phacoemulsification with two iStents versus phacoemulsification with two iStents and ECP (ICE2 procedure).

 The longitudinal retrospective study took place over 12 months, with 63 eyes receiving the ICE2 procedure and 46 eyes receiving treatment without ECP.

We evaluated IOP, best-corrected visual acuity (BCVA) and number of medications at baseline, with follow-up at 1 and 5 weeks, and 3, 6 and 12 months. The primary outcome was IOP reduction at 12 months. The results were as follows:
	
	• For the primary outcome of IOP reduction at 12 months, patients in the ICE2 group fared better. IOP decreased by 35% from medicated baseline, compared with 21% for iStent/phacoemulsification. Although the ICE2 group had higher IOPs at baseline, their final IOPs were lower (approximately 13 mmHg versus 14 mmHg).
	• Both surgeries had a very similar safety profile. At week 1, the ICE2 eyes and the iStent/phacoemulsification eyes all looked very quiet. We found no added risk to the combined procedure, and there was no delay in patients’ postoperative visual recovery in the ICE2 group.
	• Both groups had a similar reduction in medication at 12 months and similar final BCVA.
	• ECP added about 5 minutes to surgery.


	In essence, the ICE2 procedure was more effective than iStent/phacoemulsification, with no added risk. Safety was excellent in both groups.

After seeing the promising safety and efficacy of ICE2 at 1 year follow-up, I will continue to use this surgery for the appropriate patients moving forward. When we can get pressures down to 13, we know that a large proportion of patients’ glaucoma will not progress.

More studies are needed, ideally in the form of randomised trials. We need to establish whether the effect of ICE2 is sustained at 3 and 5 years.

We have already started studies that will assess the patients’ ocular surface and quality of life after MIGS, including ICE2. IOP control and disease control is the most important aspect of treatment, but the eye comfort and quality of life of our patients should not be overlooked.

1. Wellik SR, Dale EA. A review of the iStent trabecular micro-bypass stent: safety and efficacy. Clin Ophthalmol 2015;9:677-684.
	2. Guedes RAP, Gravina DM, Lake JC, et al. Intermediate results of iStent or iStent inject implantation combined with cataract surgery in a real-world setting: a longitudinal retrospective study. Ophthalmol Ther 2019;8:87-100. 
	3. Craven ER, Katz LJ, Wells JM, et al. Cataract surgery with trabecular micro-bypass stent implantation in patients with mild-to-moderate open-angle glaucoma and cataract: two-year follow-up. J Cataract Refract Surg 2012;38:1339-1345.
	4. Thomas R, Walland, M, Thomas A, Mengersen K. Lowering of Intraocular Pressure After Phacoemulsification in Primary Open-Angle and Angle-Closure Glaucoma: A Bayesian Analysis. Asia Pac J Ophthalmol (Phila). 2016 Jan-Feb;5(1):79-84.
	5. Armstrong JJ, Wasiuta T, Kiatos E, et al. The effects of phacoemulsification on intraocular pressure and topical medication use in patients with glaucoma: a systematic review and meta-analysis of 3-year data. J Glaucoma 2017;26:511–522.
	6. Friedman DS, Jampel HD, Lubomski LH, et al. Surgical strategies for coexisting glaucoma and cataract: an evidence-based update. Ophthalmology 2002;109:1902–1913.
	7. Vizzeri G, Weinreb RN. Cataract surgery and glaucoma. Curr Opin Ophthalmol 2010;21:20-24.
	8. Yip LW, Yong SO, Earnest A, et al. Endoscopic cyclophotocoagulation for the treatment of glaucoma: an Asian experience. Clin Exp Ophthalmol 2009;37:692-697.
	9. Lima FEL, Carvalho DM, Avila MP. Phacoemulsification and endoscopic cyclophotocoagulation as primary surgical procedure in coexisting cataract and glaucoma. Arq Bras Oftalmol 2010;73:419-422.
	10. Kahook MY, Lathrop KL, Noecker RJ. One-site versus two-site endoscopic cyclophotocoagulation. J Glaucoma 2007;16:527530.
	11. Francis BA, Berke SJ, Dustin L, et al. Endoscopic cyclophotocoagulation combined with phacoemulsification versus phacoemulsification alone in medically controlled glaucoma. J Cataract Refract Surg 2014;40:13131321.
	12. Lindfield D, Ritchie RW, Griffiths MF. ’Phaco-ECP’: combined endoscopic cyclophotocoagulation and cataract surgery to augment medical control of glaucoma. BMJ Open. 2012 May 30;2(3).
	13. Pantalon AD, Barata ADO, Georgopoulos M, Ratnarajan G. Outcomes of phacoemulsification combined with two iStent inject trabecular microbypass stents with or without endocyclophotocoagulation. Br J Ophthalmol. 2020 Jan 24.


	GOK RATNARAJAN, BSC, MBBS, FRCOPHTH, MD
	E: g.ratnarajan@gmail.com
	Dr Ratnarajan is a consultant ophthalmic surgeon and director of glaucoma at the Eye Unit in Queen Victoria Hospital, East Grinstead, UK. He has received honorariums from BVI.

Endoscopic cyclophotocoagulation adds cumulative advantage to MIGS

Studies show that the micropulse laser represents a safe treatment for macular disorders involving the foveal area. Further and larger studies are needed to prove the real effectiveness related to all the macular pathologies, but it can be used as an add-on to treat complex cases.

The micropulse laser represents a relatively new frontier among retinal specialists. The subthreshold energy it can deliver without damaging retinal tissue is being exploited in various macular diseases, including central serous chorioretinopathy (CSC), diabetic macular oedema (DME), and macular oedema due to branch retinal vein occlusions (BRVO).

There is increasing evidence that subthreshold micropulse laser (SML) treatment (Iridex) can serve as an additional valuable therapeutic option to intravitreal injections (anti-VEGF and/or steroids), mostly for retinal vascular diseases. And, since standardised therapies or established ‘best practice’ guidelines do not yet exist for CSC, the opportunity exists for the micropulse laser to join the armamentarium, particularly in those patients which do not tolerate eplerenone tablets. In my clinical practice, I am currently using the laser sub-threshold therapy to treat CSC both as monotherapy and in combination with systemic treatments, such as eplerenone or spironolactone.

Conventional laser photocoagulation is widely used to obtain thermal and beneficial effects on the retina; however, it can induce side effects such as chorioretinal atrophy, formation of epiretinal scars, choroidal neovascularisation and visual field defects

. The SML acts only to stimulate retinal pigment epithelium (RPE) cells to regulate different factors, such as anti-VEGF inhibitors, pigment epithelium-derived factor (PEDF) and permeability factors, sparing the neural retinal and preserving the functional integrity of the photoreceptors

 delineated well the difference between conventional laser photocoagulation and the micropulse mode. A conventional laser is characterised by the so-called continuous wave (CW) mode, in which the laser energy is delivered with a single pulse, whereas the micropulse mode delivers a train of repetitive short pulses (typically of 100–300 ms), with alternating ‘on’ and ‘off’ times.

The length of time the power is ‘on’ divided by the total time the laser is used gives rise to a ratio known as the ‘duty cycle’. The presence of the so-called ‘off’ time allows the heat to dissipate, thus minimising the thermal effect and reducing retinal injury.

As rigorously covered in recent review by Scholz et al.

, there are currently two different types of micropulse laser. The first is a diode laser with a wavelength of 810 nm, which is able to penetrate up to the choroid.

The other available SML system is the 577-nm yellow laser, which has the advantage that the xanthophyll, a pigment present in the macular layers, absorbs only a minimal amount of yellow light, thereby increasing the safety of a laser procedure close to the fovea. The development of navigated laser systems has considerably improved the accuracy and safety of the micropulse laser treatment. The eye-tracking technology minimises the eye movements of patients, and the presence of special software allows one to plan treatment based on the images obtained with fluorescein angiography (FA) and/or indocyanine angiography (ICG), optical coherence tomography (OCT) and OCT angiography.

In my hospital-based setting, I use the micropulse laser mode with a navigated system and, based on the different macular diseases, I optimise the treatment with the multimodal imaging modality. For example, in the case of CSC, I acquire the FA and ICG images where possible to evidence a typical leakage hot spot, as well as the OCT scan, to demonstrate the presence of subretinal fluid (SRF).

After taking a fundus photo of the patient’s macula, the navigated system is able to superimpose the fundus photo and the OCT/FA/ICG images, and, finally, I can perform the micropulse laser with different energies and duty-cycle at the level of the hot spot evidenced by the FA/ICG and directed to the SRF as illustrated by the OCT scan.

Before the era of anti-VEGF and intravitreal injections, laser photocoagulation was the standard treatment for DME, but severe complications such as accidental foveal damage and expansion of macular scars were observed, and so the method took a back seat. However, the recent advent of SML has provided a new age for the laser treatment of DME and researchers have sought to assess the safety and efficacy of this therapeutic approach.

 evaluated functional and morphological parameters after SML treatment with both infrared and yellow systems, showing that the lowest duty cycle (5%) setting seemed to be the safest in order to preserve the visual function and maintain the macular integrity. Moreover, Chhablani et al.

 demonstrated the safety of the two most-used subthreshold parameters (duty cycle 5% and 15%) of the yellow laser compared with conventional laser and found that the 15% duty cycle achieved better anatomical, visual and functional outcomes.

In my routine laser practice, with DME patients, I usually set the duty cycle to 10% with a power energy between 120 and 160 mW, associated with the laser-navigated treatment mode. So far, I have not had any cases of choroidal neovascularisation, photoreceptor integrity damage or laser-related visual function deterioration, which I believe demonstrates how safe the micropulse procedure is.


	Another interesting field is the application of the micropulse laser for the treatment of patients with macular oedema (MO) following an episode of BRVO. As recently summarised in a review by Eng et al.

, SML appears to be safer than conventional laser photocoagulation and is as efficacious, improving visual function and reducing the intraretinal fluid accumulation in such patients.

In a small retrospective series presented by our team at the European Society of Retina Specialists (EURETINA) congress, we analysed the safety and efficacy of the yellow navigated micropulse laser treatment in 17 patients (18 eyes) affected by MO due to BRVO with a follow-up of 3 months. We observed a statistically significant improvement of the visual acuity without a corresponding decrease in macular thickness.

Interestingly, we found that the photoreceptor structures were restored, particularly in terms of renewal of the ellipsoid zone integrity. Moreover, confirming the previous data regarding the safety of the procedure, we saw no cases of chorioretinal atrophy, scarring or choroidal neovascularisation. We had set the duty cycle to 10% and used 130 mW as medium energy with circa 600 spots at the level of the increased macular thickness (see Figure 1A–C).

Combining the micropulse laser with intravitreal injections can help to reduce the burden of numerous injections. In a recent study, Terashima et al.

 determined the efficacy and safety of the combination therapy between the yellow SML and intravitreal ranibizumab, showing that visual acuity was maintained with a decreased number of intravitreal procedures needed.

I agree with this treatment modality and in my practice I tend to combine the intravitreal approach (anti-VEGF and steroid implants) with the micropulse laser to tackle the disease in different ways, and so reduce patients’ stress and achieve the best functional result.

The standardised treatment for CSC has been the subject of debate due to the lack of data from randomised controlled trials. The first pilot study to investigate the role of micropulse laser treatment for CSC was presented in 2003

. The SML (with 810-nm diode laser) led to the complete resorption of SRF 1 month after the treatment with no recurrence at 6-month follow-up.

Since 2003, many different studies have analysed the efficacy of the micropulse laser for chronic CSC, with encouraging results. Nevertheless, the PLACE trial

, an open-label, multicentre, randomised, controlled clinical study, recently demonstrated that a significantly higher proportion of patients receiving half-dose photodynamic therapy (PDT) achieved complete resolution of SRF and functional improvement than those subjected to high-density SML (HSML).

However, in the literature there are other interesting studies which prove the efficacy of the micropulse laser for cases of CSC. For example, Kim et al.

 conducted a retrospective study with a 3-year follow-up demonstrating a complete SRF reabsorption in 81.5% of patients affected by chronic CSC who were treated with yellow 577-nm SML. 

Unlike the other published studies, which used a conventional treatment duration of 100–300 ms, the research group opted for just 20 ms, with a 15% duty cycle and a power ranging from 200 to 400 mW, applying the energy both over the area of RPE leakage and all areas of serous retinal detachment, including the fovea.

In my clinic, I follow the indications of the previous study, but slightly modifying the parameters: for the leakage point assessed by multimodal imaging modality (FA/ICG), when it is located far away from the foveal zone, I use a 15% duty cycle, 20-ms treatment duration and 300 mW of energy; whereas, for the SRF, mostly if it is localised at the foveal level, I usually use a 10% duty cycle, 20-ms duration and 150-mW energy, in order to stimulate only the RPE cells, avoiding damage to the foveal area.


	Studies show that the micropulse laser represents a safe treatment for macular disorders involving the foveal area. Regarding the efficacy, the results are not still uniform and for this reason we need further and larger studies to prove the real effectiveness related to all the macular pathologies.

In my opinion, we can currently consider the micropulse laser as an additional therapy, which may help physicians to treat disorders with complex pathophysiology, such as DME, MO due to BRVO, and CSC. The feasibility of using the micropulse laser in combination with intravitreal injections in the case of MO related to vascular disorders offers the potential to relieve the burden of injections, help with patient compliance and optimise functional outcomes.

In the case of CSC, the laser acts as another therapeutic option besides PDT with minimal risks and good efficacy, both as monotherapy and when associated with other treatment strategies, such as eplerenone and spirinolactone.

1. Seiberth V, Alexandridis E, Feng W. Function of the diabetic retina after panretinal argon laser coagulation. Graefes Arch Clin Exp Ophthalmol. 1987;225(6):385-390.
	2. Ulbig MR, Arden GB, Hamilton AP. Color contrast sensitivity and pattern electroretinographic findings after diode and argon laser photocoagulation in diabetic retinopathy. Am J Ophthalmol. 1994;117(5):583-588.
	3. Dorin G. Evolution of retinal laser therapy: minimum intensity photocoagulation (MIP). Can the laser heal the retina without harming it? Semin Ophthalmol. 2004;19:62-68.
	4. Scholz P, Altay L, Fauser S. A Review of Subthreshold Micropulse Laser for Treatment of Macular Disorders. Adv. 2017;34:1528-1555. 
	5. Vujosevic S, Martini F, Longhin E, Convento E, Cavarzeran F. Subthresold micropulse yellow laser versus subthresold micropulse infrared laser in center-involving diabetic macular: Morphologic and Functional Safety. Retina. 2015;35:1594-1603.
	6. Chhablani J , Alshareef R , Kim DT, Narayanan R,  Goud A et al. Comparison of different settings for yellow subthreshold laser treatment in diabetic macular edema. BMC Ophthalmol. 2018;18:168.
	7. Eng VA, Leng T. subthreshold laser therapy for macular oedema from branch retinal vein occlusion: focused review. Br J Ophthalmol. 2020 Feb 7 [Online ahead of print].
	8. Terashima H, Hasebe H, Okamoto F, Matsuoka N, Sato Y et al. Combination therapy of intravitreal ranibizumab and subthreshold micropulse photocoagulation for macular edema secondary to branch retinal vein occulsion: 6 month result. Retina. 2019;39:1377-1384. 
	9. Bandello F, Lanzetta P, Furlan F, Polito A. Non-visible subthreshold micropulse diode laser treatment of idiopathic central serous chorioretinopathy. A pilot study. Investig Ophtalmol Vis Sci. 2003;44:4858.
	10. van Dijk EHC, Fauser S, Breukink MB, Blanco-Garavito R, Groenewoud JMM et al. Half-dose photodynamic therapy versus high-density subthreshold micropulse laser treatment in patients with chronic central serous chorioretinopathy: the PLACE trial. Ophthalmology. 2018;125:1547-1555.
	11. Kim YJ, Kim SY, Ha S, Moon D, Seong S et al. Short-duration multiple-session subthreshold micropulse yellow laser (577 nm) for chronic central serous chorioretinopathy: results at 3 years. Eye (Lond). 2019;33:819-825.


	EMILIANO DI CARLO, MD
	E: emi.dicarlo@hotmail.it
	Dr Di Carlo is a vitreoretinal consultant at the ophthalmology department of the StÃ¤dtisches Klinikum Karlsruhe, Germany. His main interests are micropulse laser and new frontiers of vitreoretinal surgery. He has no financial interests in the subject matter.

CAMILLA SIMINI, MD
	E: camilla.9128@gmail.com
	Dr Simini is an ophthalmology resident at StÃ¤dtisches Klinikum Karlsruhe, Germany, which is directed by Prof. A.J. Augustin. Her main interests are: medical and surgical retina. She has no financial disclosures.

A new frontier in micropulse laser treatment for retinal disorders

When paired with multifocal extended depth-of-field technology, the new, small aperture ocular IOL, IC-8, delivers excellent extended depth of focus at near, far and intermediate ranges whilst reducing halo and glare.

A new small-aperture ocular IOL, IC-8 (Acufocus), which is CE Marked and currently under investigation by the United States Food and Drug Administration (FDA) employs the pinhole camera effect to correct presbyopia. By flattening the defocus curve on both the myopic and hyperopic sides, the IOL essentially creates a small amount of myopia, thereby extending the patient’s depth of focus and eliminating visual effects from corneal astigmatism or other irregularities.

This high-technology, one-piece hydrophobic acrylic ocular implant comprises an embedded opaque annular mask with a central aperture. Aligned light rays converge through the 1.36-mm central aperture, while peripheral defocused and, often, aberrated rays are blocked from disrupting the image.

As a result, patients experience a continuous range of vison from near to far, including the increasingly important intermediate range. At 1.5- to 7-feet away, the intermediate range represents a critical zone of activity for most people. It is where we eat most of our meals, do our desk work and watch the majority of our large-screen media. It is where many people earn their livings, including refractive surgeons.

Originally intended to be paired with a monofocal IOL, it has been found that, when paired with a multifocal IOL, the IC-8 is better than previous alternatives at enhancing visual acuity at intermediate distances, and so has the potential to benefit this underserved cohort. Likewise, patients who have had previous refractive procedures are becoming more common.

As they proliferate, so does our necessity for techniques and technologies tailored to support their special needs. The IC-8 has shown good outcomes in these ‘veteran’ surgical patients.

Surgeons are only now beginning to appreciate the additional benefits made possible by combining the small-aperture lens with IOLs that function on completely different optical principles. Experimentation is ongoing, and this novel strategy may ultimately lead us to maximise the full potential of the IOL, providing patients with truly satisfying customised outcomes.

LOW-ADD MIOLS 
	Low-add multifocal lenses (MIOLs) have been shown to improve intermediate visual acuity and offer surgeons the ability to further individualise patients’ visual outcomes, particularly when mixed with another refractive technology. Combining a multifocal lens with a different type of lens also can act to minimise glare and halo, an intrinsic characteristic of MIOL optics.

It is well known that most types of presbyopia-correcting IOLs-including multifocal refractive and diffractive, and even the newest trifocal technology-sacrifice distance vision to some extent in order to correct near vision and induce a variable amount of dysphotopsias.

 One study of the AcrySof ReSTOR +2.50 D IOL (Alcon) found it provided good intermediate and functional near vision for patients who did not want to accept the higher potential for visual disturbances associated with the +3.00 D version of the same IOL, but wanted more near vision than a monofocal IOL generally provides.

Another prospective comparative investigation evaluated bilateral cataract surgery using the +3.00 D AcrySof IOL or a +4.00 D power of the implant.

 The +3.00 D IOL provided superior uncorrected distance visual acuity, significantly better uncorrected intermediate visual acuity at 40, 50, 60 and 70 cm, and functional reading acuity at 38.9 cm. Eyes with the +3.00 D IOL had better intermediate vision than those with the +4.00 D model without compromising distance and near visual acuity.

MF EXTENDED DEPTH OF FOCUS
	The Lentis Mplus LS-313 MF20 (Teleon; available in Europe but not in the US) is a foldable, one-piece, aspherical multifocal posterior chamber IOL that extends a patient’s depth of focus. Its refractive rotationally asymmetric design helps minimise the loss of light to below approximately 7%, thereby improving contrast and retinal image quality.

An evaluation of the implant, with +2.00 D of near add compared with +3.00 D, found superior visual outcomes from far distance to a near of about 25 cm with the latter lens. The +2.00 D demonstrated excellent visual results from far distance to an intermediate distance of about 50 cm.

Unlike the aforementioned multifocal implants, the IC-8 IOL functions due to the pinhole effect: by reducing scattered light and permitting only parallel rays to reach the macula, depth of focus is extended and visual disturbances such as glare and halo are reduced. Small-aperture technology can even overcome problems with corneal asphericity and irregularities. Astigmatism up to 1.50 D can be corrected with the lens alone.

Typically, the IC-8 IOL is implanted in the non-dominant eye, with a monofocal lens in the contralateral eye. To enhance acuity, the small-aperture IOL can be paired with other technologies, such a multifocal, a low-add multifocal or even a trifocal lens. There are many combinations to consider, with the basic idea being that using different types of implants can enhance the sharpness of vision at near, intermediate and distance, and minimise the side effects of the competing technologies.


	The ongoing prospective, multicentre Mosiac study was undertaken to evaluate visual outcomes from the combination of the IC-8 IOL and the Lentis LS-313 MF-20.

 Our group presented 5-month follow-up data on 13 patients with bilateral implantation of the IC-8 IOL with the Lentis LS-313 MF-20 with +2.00 D of near add. We looked at parameters including:

Uncorrected and corrected (binocular) far, intermediate and near visual acuity;

Photic phenomena (halo and glare simulator).

Included were the 26 eyes of 13 patients with cataracts whose average age was 68.5±10.8 years. The targeted refraction for the IC-8 IOL eyes was –0.43±0.18 D with an achieved refraction of 0.42±0.41 D.

The achieved refraction was within ±0.50 D 62% of the time. The targeted refraction for the MF-20 eyes was –0.15±0.16 D and the achieved refraction was –0.33±0.42 D. The achieved refraction was within ±0.50 D 85% of the time.

We found that patients had excellent binocular visual acuity at far and intermediate distances, as well as functional vision at near. Furthermore, they had functional reading acuity at near and intermediate distances, and there was a comparatively low incidence of photic phenomena (see Figures 1 and 2). The combination of the small-aperture implant with a low-add multifocal lens like the Lentis LS-313 MF-20 is a good treatment option for patients who are motivated to achieve spectacle independence.

Multifocal lens designs can exhibit pronounced peaks and troughs, but the IC-8 IOL provides uninterrupted functional vision over 3.00 D of defocus.

 The small-aperture principle has the ability to produce a high-quality full range of vision without blurry zones, and it is more forgiving of refractive error misses or surprises.

The implant has been shown to provide good visual outcomes in post-LASIK and post-RK eyes

, making it an attractive option for patients who previously could not find an appropriate presbyopia-correcting IOL. Likewise, patients with corneal irregularities can benefit from the technology’s ability to reduce aberrations.

When paired with multifocal extended depth-of-focus (EDOF) technology, the IC-8 delivers excellent EDOF at near, far and intermediate ranges whilst reducing halo and glare. It can enhance the physician’s ability to customise successful visual outcomes for each patient, even for those who have undergone previous refractive surgeries. Based on the simple, proven and ancient understanding of the pinhole’s effect on light ray alignment, this IOL is a versatile tool to help cataract patients achieve their paramount postoperative visual goals.

1. Gundersen KG, Potvin R. Comparative visual performance with monofocal and multifocal intraocular lenses. Clin Ophthalmol. 2013;7:1979-1985.
	2. de Vries NE, Webers CA, MontÃ©s-MicÃ³ R, Ferrer-Blasco T, Nuijts RM. Visual outcomes after cataract surgery with implantation of a +3.00 D or +4.00 D aspheric diffractive multifocal intraocular lens: Comparative study. J Cataract Refract Surg. 2010;36(8):1316-1322.
	3. Linz K, Attia MS, Khoramnia R, et al. Clinical evaluation of reading performance using the Salzburg Reading Desk with a refractive rotational asymmetric multifocal intraocular lens. J Refract Surg. 2016;32(8):526-532.
	4. Venter JA, Pelouskova M, Bull CE, et al. Visual outcomes and patient satisfaction with a rotational asymmetric refractive intraocular lens for emmetropic presbyopia. J Cataract Refract Surg. 2015;41(3):585-593.
	5. Calvo-Sanz JA, SÃ¡nchez-Tena MA. Characterization of optical performance with defocusing curve: Analysis of two refractive intraocular lens models with high and medium addition. J Optom. 2018 Oct 31.
	6. https://www.healio.com/ophthalmology/cataract-surgery/news/online/%7B2809ee76-e466-43fe-b70b-dd94ff661925%7D/video-edof-iol-using-pinhole-effect-lessens-ocular-effects.
	7. Dick HB, Elling M, Schultz T. Binocular and monocular implantation of small-aperture intraocular lenses in cataract surgery. J Refract Surg. 2018;34(9):629-631.
	8. Dick HB. Small-aperture strategies for the correction of presbyopia. Curr Opin Ophthalmol. 2019;30(4):236-242.

GERD U. AUFFARTH, MD, FEBO
	E: auffarthg@aol.com
	Prof. Auffarth is chairman and medical director of the Department of Ophthalmology of the University Clinic of Heidelberg, Heidelberg, Germany, director of the David J. Apple, MD International Laboratory of Ocular Pathology, and director of the International Vision Correction Research Center in Heidelberg. He receives research grants and lecture fees from Alcon, Johnson and Johnson, Zeiss, Hoya, Oculentis, Rayner, Acufocus, KOWA and Biotech.

How pinhole camera effect in small-aperture implant corrects presbyopia

It is important to proactively consider night-time dryness as its own separate entity. An effective lid hygiene regime will minimise the risk of build-up of deposits on compromised lid margins and thus optimise long term success and tolerance in these patients.

The awareness of the high incidence, impact on daily life and challenges of treating dry eye disease (DED) has increased exponentially over the past 2-3 decades. Significant progress towards achieving consistency in understanding the fundamental causes of the condition, the systematic strategies used for diagnosis and stepwise treatment approaches have undoubtedly come from the two landmark Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop – DEWS I and II – reports.

However, with such strength of guidance, it is also easier for some practitioners to fall into a generic blanket approach. This can result in patients’ history being taken in a less focused manner, and the more subtle clinical findings receiving too little attention.

Due to the robustness of the fundamental recommended treatment steps, the majority of patients are still likely to experience significant benefit, often accepting the improved but residual symptoms as inevitable. However, this is not the same as providing the most comprehensive and appropriate care.

A proportion of DED patients will experience worsening of symptoms overnight or on waking, even with effective warm compresses, lid massage/cleaning, preservative free lubricants and oral omega-3 supplements. Although this may just be an unavoidable component of their dry eye condition, it is imperative to proactively consider night-time dryness as a separate entity.

Ophthalmologists should differentiate between worsening of dry eyes later in the day, typically associated with visual concentration tasks, and worsening of symptoms once the patient has gone to sleep and awakes in the morning. The former is common in all dry eye patients, whilst the latter is more commonly related to night dryness.

Several natural bodily occurrences take place during the night which can result in fewer nutrients reaching the ocular surface: body temperature drops, metabolism slows

, tear production lessens and active blinking does not take place.  Most young healthy patients will cope with this, but in those with existing DED or in older patients, there is likely a reduced reserve to be able to tolerate that same drop, thus resulting in increased symptoms.

In patients with inferior localised, linear corneal+/- conjunctival staining despite compliance with treatment, it is important to consider two key elements. In patients with significant, poorly controlled lid margin inflammation, this staining may be the result of direct contact toxicity from the lower lid margin to the ocular surface. However, the possibility of nocturnal lagophthalmos is something that must be proactively considered and evidence of the same specifically looked for.

Although more severe lagophthalmos may require surgical intervention, the majority of patients we see in practice will not need this. Simple exercises to encourage active, firm blinking and massage of the upper lid to enhance closure can very quickly translate to subjective and objective improvements.

The use of tape to keep the lids closed at night can be very effective, but this is not particularly practical in older populations who are more likely to need to get up during the night than younger patients. It is with these patients that the use of ointments at night can tip the balance of control back in our favour – but it is important to consider the optimal qualities desired.

The fact that ointments are thick and viscous provides prolonged dwell times in the eye, coating the ocular surface and also aiding the lids to ‘stick’ together – but this same positive quality can also create further problems if the wrong substances are kept in contact with an already compromised ocular surface for extended periods.

The need to choose a preservative-free option is obvious. The majority of ointments are paraffin-based, which provides effective lubrication with a very low risk of adverse reactions. Some may contain lanolin,

 which is believed to aid aqueous absorption and reduce evaporation but is also avoided by some ophthalmologists due to it being a potential allergen.

Phosphate must be avoided, since the risk of calcification would be even greater with the prolonged contact time of an ointment,

 whilst the addition of vitamin A, as a natural component of the tear film important for mucosal and goblet cell health, is likely to aid recovery of the compromised ocular surface.

Finally, I always reiterate to patients the importance of a consistent and effective lid hygiene regime, specifically in the context of using an ointment, to minimise the risk of build-up of deposits on these compromised lid margins and thus further optimise long term success and tolerance.

Saj H. Khan, M.B.B.S (London), FRCSEd (Ophth)
	E: sajkhan@scopeophthalmics.com
	Mr Khan is a consultant ophthalmic surgeon. He consults in Caterham, Croydon, Epsom/Ashtead as well as in Harley Street, London, UK. Mr Khan is a council member of United Kingdom & Ireland Society of Cataract and Refractive Surgeons (UKISCRS) and the British Society of Refractive Surgery (BSRS). He is also a member of European Society of Cataract and Refractive Surgeons (ESCRS).
	He has financial interests with Scope and BVI.

1. https://www.tearfilm.org/dewsreport/pdfs/TOS-0502-DEWS-noAds.pdf
	2. https://www.tfosdewsreport.org/report-tfos_dews_ii_report/36_36/en/
	3. Sharma S, Kavuru M. Sleep and metabolism: an overview. Int J Endocrinol. 2010;270832. doi:10.1155/2010/270832
	4. https://www.medicines.org.uk/emc/files/pil.3538.pdf
	5. https://emedicine.medscape.com/article/1194813-overview#a6
	6. https://iovs.arvojournals.org/article.aspx?articleid=2378794

When daydreaming in clinic, think about night-time dry eye

Clinical studies are underway to confirm the promising results obtained so far with subretinal implantation of human amniotic membrane plugs in the treatment of large and recurrent macular holes.

Macular holes (MHs) are tears in the retina’s fovea centralis, and can be acquired, acute or subacute, spontaneous or traumatic. They can cause the severe deterioration of eyesight if left untreated. 

Since our clinical practice in the ophthalmology unit of the StÃ¤dtisches Klinikum in Karlsruhe is one of the largest medical centres in the southwest region of Germany, we encounter and treat a significant number of patients affected by this disorder.

Recent, novel surgical methods in the management of MHs offer the chance to improve visual acuity in patients with large or recurrent holes who would otherwise be doomed to lose vision in the affected eye. Following a short overview of MHs, this article provides an update on surgical treatment approaches.

The first description of MHs dates back to Hermann Knapp in 1869,1 who reported them as resulting from direct blunt ocular trauma. Patients with MHs without a history of eye trauma were increasingly observed, and by 1970, only 5–10% of them were ascribed to trauma, with the rest considered idiopathic.2 Presently, the vast majority of MHs are attributed to vitreomacular traction.3

Clinical suspicion is confirmed by slit-lamp fundoscopic examination, which shows a well-defined round or oval lesion in the macula with yellow-white deposits at the base.1 Optical coherence tomography (OCT) confirms the diagnosis and allows the lesion to be classified into one of Gass’ four stages.

Ophthalmologists Neil E. Kelly and Robert T. Wendel described the first modern surgical approach to MHs in 1991. This technique is still used today and is standard procedure for holes under 400 µm in diameter.
	The procedure consists of the following stages:

An extensive 23- to 27-gauge pars plana vitrectomy;

Detachment of the posterior vitreous cortex with internal limiting membrane (ILM)-peeling;

Epi-retinal membrane (ERM) peeling around the hole and thorough fluid–gas exchange (gas tamponade);

Followed by postoperative face-down positioning.4

The preoperative diameter of the MH plays an important role in choosing the best surgical technique and in predicting postoperative closure of the hole and visual outcome.5,6 It is therefore advisable to consider the need to accurately measure the width of each hole with an OCT caliper before choosing the surgical approach. Indeed, for all types of vitreoretinal surgery, a good preoperative strategy helps to achieve the best outcome.

A study published in Ophthalmology in 2010 described the classic ILM-flap technique,7 and it was subsequently revised in 2015, when the temporal-inverted-ILM-flap technique was introduced. With this method, following core vitrectomy and dye staining, the ILM is not completely removed from the retina but is left in place, attached to the edges of the MH.

This ILM remnant is then inverted to cover and fill the MH. Finally, fluid–air exchange is performed.8 According to another study, which compared the use of inverted ILM-flap, free-flap and conventional ILM peeling, although all techniques showed a tendency towards visual improvement, the inverted-flap technique seemed to induce a faster and more significant recovery in the short term.9

From our point of view, despite the optimal anatomical results, it remains unclear as to how good a substrate the ILM-flap is for the remodelling of the neuro-sensitive retina, given the fibrogenic potential of the ILM plug and the uncertainty as to the role fibrotic proliferation may play in restoring visual function.

Until recently, our surgical approach for large and recurrent MHs was to inject autologous whole blood of the patient into the macular defect: a three-port 23-gauge pars plana vitrectomy was undertaken and the central portion of the retina coloured with indocyanine green. ILM peeling then took place with the help of scraper and thumb forceps.

A partial fluid–air exchange followed, as well as the injection of one to two drops of blood. After aspiration of excessive fluid and blood, the surgery was completed with a low-density silicon oil tamponade. Anatomical results using this technique were relatively satisfying but functional ones controversial.

Interestingly, Purtskhvanidze et al. compared both anatomical and functional success when using platelet concentrate or whole blood to induce closure of persistent MHs. Their results indicated that the former approach seemed to give better results.10

In particularly large or recurrent MHs in which the ILM has already been removed during previous surgery, transplantation may offer a solution to close the holes. A study published in 2016 reported using the lens capsule in an attempt to close MHs, with promising results.11

Another autologous transplant was then introduced. It consisted of a neurosensory peripheral retinal transplant, followed by tamponade: either silicone oil tamponade, or short-term perfluoro-n-octane heavy-liquid tamponade. Anatomical results were good but success in postoperative visual acuity was limited.12

A novel, less invasive alternative to autologous tissue transplantation in the surgical treatment of large and recurrent MHs is the use of human amniotic membrane (hAM) transplantation (or implantation). With this method, the lens capsule and the peripheral retina of the affected eye are left intact. A plug of lyophilised or cryopreserved hAM is used instead of the patients’ tissues to repair the MH.

Use of hAM in medicine is not new. Applications of hAM in medicine in general, and in surgical ophthalmology in particular, have been reviewed.13 Until 2018, the use of hAM in clinical ophthalmology had been confined to the ocular surface.

In one study published in 2018, hAM patches were placed via an intraocular approach to repair large and recurrent MHs.14 Interestingly, from a historical point of view, repair of MHs with hAM had already been attempted in the mid 20th century, with a surgically complicated retro-bulbar approach in 1957 and in 1964.15,16

 experiments preceded present day clinical use of hAM. Experiments carried out in pigs’ eyes showed the effect of transplanted amniotic membrane on subretinal wound healing.

Amniotic membrane modified choroidal neovascularisation after mechanical damage to Bruch’s membrane and seemed to behave as a basement membrane substitute for the proliferation of retinal pigment epithelium (RPE).17 

, it was demonstrated that RPE cells cultured on hAM had an epithelial phenotype and secreted growth factors essential for retinal homeostasis.18

A 2018, prospective, consecutive case-series described positive results when hAM was implanted in eight patients who had large recurrent MHs. All patients had already undergone pars plana vitrectomy with ILM peeling and gas tamponade. The hAM was delivered cryopreserved from a human tissue bank and was defrosted intraoperatively before insertion. 

In all patients, OCT at 1 week postoperatively showed MH closure with neurosensory retina overfilling the hAM. Best corrected visual acuity improved from 1.48±0.49 logarithm of the minimal angle of resolution (logMAR), (20/800) preoperatively to 0.71±0.37 logMAR (20/100) 3 months postoperatively, and to 0.48±0.14 logMAR (20/50) 6 months after the procedure. No ophthalmological adverse events were seen during follow-up.14

In a further study, hAM was used in ten patients with high myopia and MHs associated with retinal detachment who had undergone at least one pars plana vitrectomy. Half of the patients received silicon oil and half 10% octafluoropropane as tamponade at the end of surgery.

Silicon oil was removed 2 months after surgery. Results were very satisfying since retinal re-attachment was achieved in all patients and visual acuity improved from 1.73 logMAR to 0.94 logMAR after 6 months.19

It appears that hAM is well tolerated. The possibility of hAM rejection has also been considered. In 1999, subretinal implantation of hAM in a rabbit model caused no evidence of inflammation or rejection.20

In the wake of these results, we started implanting amniotic membranes in patients who had large or recurrent MHs. However, a few of the steps in our surgical approach differs from that described by the aforementioned study: like them, we use a 23-gauge access but unlike their approach, we do not use a chandelier, so the method is not bi-manual. The amniotic membrane is managed with a crocodile forceps.

A partial fluid–air exchange takes place, leaving a minimal amount of fluid at the foveal level in order to facilitate the manoeuvre of insertion of the amniotic plug. Implantation of the membrane may be facilitated by the use of a Tano scraper. No perfluorocarbon (PFCL) is used. Surgery is completed with fluid–air exchange and, finally, wash-out with perfluoropropane takes place.

The best possible outcome, in terms of anatomical results as well as visual acuity, is achieved when patients are able to remain in a face-down position for several days. In those who have physical disabilities or high comorbidities and who are, therefore, unable to hold the face-down position for a long time, silicon oil is used to keep the amniotic membrane in place after insertion.

Clinical studies are currently underway to confirm the promising results obtained so far with subretinal implantation of hAM plugs in the treatment of large and recurrent MHs. It seems that, in addition to anatomical success, the amniotic membrane stimulates retinal ingrowth and leads to improvements in visual acuity.

For this reason, we think attempts should be made to further the understanding of this novel technique in order to analyse its capability to restore visual function. We would suggest an accurate comparison of preoperative and postoperative measured parameters such as visual field assessment and electroretinogram exams, which can validate this technique. In conclusion, we would affirm that the implantation of amniotic membrane may offer new hope in restoring vision in patients with an otherwise grim outlook.

E: emi.dicarlo@hotmail.it
	Dr Di Carlo is a vitreoretinal consultant at the ophthalmology department of the StÃ¤dtisches Klinikum Karlsruhe, Germany. His main interests are micropulse laser and new frontiers of vitreoretinal surgery. He has no financial interests in the subject matter.

1. Knapp, H. Ãber isolierte Zerreissungen der Aderhaut infolge von Traumen auf dem Augenapfel. Arch Augenheilkunde. 1869;1:6-29.
	2. Aaberg, TM. The macular holes. A Review. Surv Ophthalmol. 1970;15:139-162.
	3. Stalmans P, Benz M, Gandorfer A et al. Enzymatic vitreolysis with ocriplasmin for vitreo-macular traction and macular holes. New Engl J Med. 2012;367:606-615.
	4. Kelly NE, Wendel RT. Vitreous surgery for idiopathic macular holes. Results of a pilot study. Arch Ophthalmol. 1991;109:654-659.
	5. Tadayoni R, et al. Relationship between macular hole size and the potential benefit of internal limiting membrane peeling. Br J Ophthalmol. 2006;90:1239-1241.
	6. Ullrich,et al. Macular hole size as a prognostic factor in macular hole surgery. Br J Ophthalmol. 2002;86:390-393.
	7. Michalewska, et al. Inverted internal limiting membrane flap technique for large macular holes. Ophthalmology. 2010;117:2018-2025.
	8. Michalewska, et al. Temporal inverted internal limiting membrane flap technique versus classic inverted internal limiting membrane flap technique: a comparative study. Retina. 2015;35:1844-1850.
	9. Velez-Montoya R, et al. Inverted ILM flap, free ILM flap and conventional ILM peeling for large macular holes. Int J Retina Vitreous. 2018;19:8.
	10. Purtskhvanidze K, et al. Persistent full-thickness idiopathic macular hole: anatomical and functional outcome of revitrectomy with autologous platelet concentrate or autologous whole blood. Ophthalmologica. 2017;239;1:19-26
	11. Chen SN, et al. Lens capsular flap transplantation in the management of refractory macular hole from multiple etiologies. Retina. 2016;36:163-170.
	12. Grewal, et al. Autologous neurosensory retinal free flap for closure of refractory myopic macular holes. JAMA Ophthalmol. 2016;134:229-230.
	13. Murube J. Early clinical use of amniotic membrane in medicine and ophthalmology. The Ocular Surface. 2006;4:114-119.
	14. Rizzo, et al. A human amniotic membrane plug to promote retinal breaks repair and recurrent macular hole closure. Retina. 2018. doi.org/10.1097/IAE.0000000000002320.
	15. Csapody I. Amnion Implantation gegen Maculaloch (Amniotic membrane implantation against macular holes). Ophthalmologica, 1957;134:273-275.
	16. Bechrakis E, Soellner F. Zur Amnion Implantation bei Makulaforamen [On amnion implantation in macular foramina.] Ber Zusammenkunft Dtsch Ophthalmol Ges. 1964;65:81-83.
	17. Kiilgaard JF, et al. Transplantation of amniotic membrane to the subretinal space in pigs. Stem Cells Int, 2012. Doi.org/10.1155/2012/716968.
	18. Ohno-Matsui K, et al. The effects of amniotic membrane on retinal pigment epithelial cell differentiation. Mol Vis. 2005;6:1-10.
	19. Caporossi T, et al. A human Amniotic Membrane plug to manage high myopic macular hole associated with retinal detachment. Acta Ophthalmol. 2019.doi.org/10.1111/aos.14174
	20. Rosenfeld PJ, et al. Subretinal implantation of human amniotic membrane: a rabbit model for the replacement of Bruch’s membrane during submacular surgery. Invest Ophthalmol Vis Sci. 1999;40:206.

Human amniotic membrane in the surgery of recurrent macular holes

Gonioscopy-assisted transluminal trabeculotomy (GATT) has been shown to be successful in the management of both primary and secondary open-angle glaucoma. Patient selection and management of expectations is key.

Gonioscopy-assisted transluminal trabeculotomy (GATT) is an ab interno, minimally invasive glaucoma surgery introduced by Dr Ronald Fellman in 2014.1 It aims to circumferentially incise the inner wall of Schlemm’s canal (SC), in order to connect it directly to the anterior chamber.

The procedure is performed through two clear corneal incisions, under gonioscopic view. An illuminated microcatheter or a prolene suture is introduced into SC through a goniotomy incision and threaded using 23 g microsurgical forceps, coursing circumferentially throughout the entire canal, until it reappears from the opposite cut end of SC. Both ends are then pulled out, creating a 360° incision, cleaving the entire trabecular meshwork (Figure 1).

GATT has been shown to be successful in the management of both primary and secondary open-angle glaucoma, particularly in steroid-induced glaucoma.2 It has also demonstrated effectiveness in paediatric glaucoma and in eyes with a history of previous incisional procedures, including trabeculectomy and glaucoma drainage devices.3

Like most angle-based procedures, GATT requires the surgeon to be familiar with intraoperative gonioscopy and angle structures. These can be practised in a wetlab and/or intraoperatively after phacoemulsification.

Once the surgeon is comfortable with goniosurgery, the procedure itself has a moderate learning curve. Once mastered, it becomes a safe and cost-effective surgical option to lower intraocular pressure (IOP), as well reduce dependence on glaucoma-lowering medications.

It is minimally invasive – performed through two corneal paracentesis – and does not involve leaving a device inside the eye.

It addresses the juxtacanalicular outflow pathway, known to have the highest resistance to aqueous outflow, thus restoring flow through the eye’s natural drainage system, rather than creating an alternative pathway into the subconjunctival space.

It does not violate the conjunctiva; hence, it does not compromise the results of any future bleb-based glaucoma surgeries. It also avoids the risks associated with bleb-based procedures, e.g., hypotony, infection and dysthesia.

The 360° incision directs flow into more collector channels, especially through the inferonasal quadrant, which is known to have a higher distribution of collector channels.4

It is a low-cost procedure, as it can be performed using a prolene suture.

As with any surgical procedure, proper patient selection is key to success. Patients with a bleeding tendency, corneal opacities that impede proper visualisation of the angle, and eyes with narrow angles are poor candidates for GATT.

GATT may be avoided in poorly compliant patients with advanced glaucoma, where a trabeculectomy or tube surgery may have a better chance of putting the patient off medications.

GATT is expected to lower the IOP by around 30–50%,5 and the number of glaucoma-lowering medications by one to two. There is some evidence that it is more effective in secondary compared with primary open-angle glaucoma.

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Human amniotic membrane in the surgery of recurrent macular holes

Pearls for conducting GATT in open-angle glaucoma

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