European Glaucoma Society - A guide on surgical innovation for glaucoma.

PROLOGUE: Glaucoma surgery has been, for many decades now, dominated by the universal gold standard which is trabeculectomy augmented with antimetabolites. Tubes also came into the scene to complement what we use to call conventional or traditional glaucoma surgery. More recently we experienced a changing glaucoma surgery environment with the "advent" of what we have become used to calling Minimally Invasive Glaucoma Surgery (MIGS). What is the unmet need, what is the gap that these newcomers aim to fill? Hippocrates taught us "bring benefit, not harm" and new glaucoma techniques and devices aim to provide safer surgery compared to conventional surgery. For the patient, but also for the clinician, safety is important. Is more safety achieved with new glaucoma surgery and, if so, is it associated with better, equivalent, or worse efficacy? Is new glaucoma surgery intended to replace conventional surgery or to complement it as an 'add-on' to what clinicians already have in their hands to manage glaucoma? Which surgery should be chosen for which patient? What are the options? Are they equivalent? These are too many questions for the clinician! What are the answers to the questions? What is the evidence to support answers? Do we need more evidence and how can we produce high-quality evidence? This EGS Guide explores the changing and challenging glaucoma surgery environment aiming to provide answers to these questions. The EGS uses four words to highlight a continuum: Innovation, Education, Communication, and Implementation. Translating innovation to successful implementation is crucially important and requires high-quality evidence to ensure steps forward to a positive impact on health care when it comes to implementation. The vision of EGS is to provide the best possible well-being and minimal glaucomainduced visual disability in individuals with glaucoma within an affordable healthcare system. In this regard, assessing the changes in glaucoma surgery is a pivotal contribution to better care. As mentioned, this Guide aims to provide answers to the crucial questions above. However, every clinician is aware that answers may differ for every person: an individualised approach is needed. Therefore, there will be no uniform answer for all situations and all patients. Clinicians would need, through the clinical method and possibly some algorithm, to reach answers and decisions at the individual level. In this regard, evidence is needed to support clinicians to make decisions. Of key importance in this Guide is to provide an overview of existing evidence on glaucoma surgery and specifically on recent innovations and novel devices, but also to set standards in surgical design and reporting for future studies on glaucoma surgical innovation. Designing studies in surgery is particularly challenging because of many subtle variations inherent to surgery and hence multiple factors involved in the outcome, but even more because one needs to define carefully outcomes relevant to the research question but also to the future translation into clinical practice. In addition this Guide aims to provide clinical recommendations on novel procedures already in use when insufficient evidence exists. EGS has a long tradition to provide guidance to the ophthalmic community in Europe and worldwide through the EGS Guidelines (now in their 5th Edition). The EGS leadership recognized that the changing environment in glaucoma surgery currently represents a major challenge for the clinician, needing specific guidance. Therefore, the decision was made to issue this Guide on Glaucoma Surgery in order to help clinicians to make appropriate decisions for their patients and also to provide the framework and guidance for researchers to improve the quality of evidence in future studies. Ultimately this Guide will support better Glaucoma Care in accordance with EGS's Vision and Mission. Fotis Topouzis EGS President

Fellow of the European board of ophthalmology glaucoma examination and diploma (FEBOS-Gl): update on 8 years of experience and future perspectives.

Glaucoma is the leading cause of irreversible blindness worldwide. Early diagnosis and appropriate management of the disease are essential to avoid a significant impact on the quality of life of millions of patients and the socioeconomic impact on societies. Education is the hallmark of good medical care. The European Glaucoma Society (EGS) has dedicated significant efforts to provide means of improving education, training, and testing knowledge in the field of glaucoma. The Fellow of the European Board of Ophthalmology Subspecialty (FEBOS)-Glaucoma examination, introduced and organized yearly by the EGS since 2015 in collaboration with the European Board of Ophthalmology (EBO), has become a valuable tool for increasing overall knowledge in the field. Over the 8 years of experience, several updates and new projects have emerged around the examination to further increase the overall quality of education, training, and knowledge in the field of glaucoma in Europe, particularly in UEMS and associated countries. This article discusses in detail the various projects and measures introduced by the EGS.

A COVID-19-Related Retinopathy Case Report.

The recent outbreak of the severe acute respiratory syndrome coronavirus-2 has been declared a worldwide pandemic by the WHO. Within various multi-organ involvements, several ocular manifestations have been described. We report the case of a patient diagnosed with COVID-19 who presented with a progressive increase of bilateral cotton wool spots over a 1-week period, despite quick and complete recovery of systemic signs of the disease and no ocular symptoms. We followed the evolution of such lesions over a 3-month period. Here, we underline the importance of retinal screening even if no ocular symptom is reported. Furthermore, we demonstrate the essential role of fundus examination as a reflection of systemic vascular changes.

Retinal Manifestations in Patients with COVID-19: A Prospective Cohort Study.

The recent outbreak of the Coronavirus SARS-CoV-2 has been declared a worldwide pandemic. Within various multi-organ involvement, several ocular manifestations have been described, such as conjunctivitis and retinopathy. The prevalence and severity of retinal lesions and their relation to the severity of the systemic disease are unknown. We performed a prospective, observational study on 172 consecutively hospitalized patients with acute confirmed COVID-19 infection. All patients underwent screening widefield fundus photography at the time of hospital admission. Despite no ocular or vision-related symptoms, we found cotton wool spots (CWS) and/or hemorrhages in 19/172 patients (11%). Diabetes history, overweight, and elevated C-reactive protein were more frequently observed among patients with retinal abnormalities, while a history of systemic hypertension was more frequently observed among patients without retinal findings. At a 3-month follow-up visit, CWS had subsided in all patients.

Age-related changes in the fractal dimension of the retinal microvasculature, effects of cardiovascular risk factors and smoking behaviour.

PURPOSE: This cross-sectional study investigates the association between retinal vessel complexity and age and studies the effects of cardiovascular health determinants. METHODS: Retinal vessel complexity was assessed by calculating the box-counting fractal dimension (Df ) from digital fundus photographs of 850 subjects (3-97 years). All photographs were labelled as 'non-pathological' by the treating ophthalmologist. RESULTS: Statistical models showed a significantly decreasing relationship between age and Df (linear: R-squared = 0.1897, p < 0.0001; quadratic: R-squared = 0.2343, p < 0.0001; cubic: R-squared = 0.2721, p < 0.0001), with the cubic regression model offering the best compromise between accuracy and model simplicity. Multivariate cubic regression showed that age, spherical equivalent and smoking behaviour have an effect (p < 0.0001) on Df . A significantly increasing effect of the number of pack-years on Df was observed (effect: 0.0004, p = 0.0017), as well as a significantly decreasing effect of years since tobacco abstinence (effect: -0.0149, p < 0.0001). CONCLUSION: We propose using a cubic trend with age, refractive error and smoking behaviour when interpreting retinal vessel complexity.

Comparison of preserved bimatoprost 0.01% with preservative-free tafluprost: A randomised, investigator-masked, 3-month crossover, multicentre trial, SPORT II.

IMPORTANCE: This study compares the efficacy and tolerability of a preservative-free prostaglandin analogue (tafluprost 15 mg/ml) to a prostaglandin analogue that uses 0.02% of benzalkonium chloride (bimatoprost 0.1 mg/ml). BACKGROUND: Different prostaglandin analogues have been commercially approved, with differences in tolerability. DESIGN: Prospective, randomised, investigator-masked, 3-month crossover, multicentre trial. PARTICIPANTS: Sixty-four patients with ocular hypertension or open-angle glaucoma were randomised to two groups, after a 4-week washout period from their current topical drop regimen. METHODS: Participants were randomised to tafluprost (Group 1; n = 33) or bimatoprost (Group 2; n = 31). At month 3, each group switched to the opposite treatment. IOP was evaluated at multiple timepoints. MAIN OUTCOME MEASURES: The primary outcome was difference in mean IOP between the two groups at the final visit. Secondary outcomes included change from baseline IOP at month 3 and month 6, difference in mean IOP at month 3 and difference in IOP at all timepoints. Safety outcomes included best-corrected visual acuity (BCVA), adverse events, ocular tolerability, optic nerve assessment and slit lamp biomicroscopy. RESULTS: Both medications significantly lowered IOP at month 6 compared to baseline: 5.4 mmHg (27%) for tafluprost and 6.8 mmHg (33%) for bimatoprost (p < 0.0001). No significant differences in any of the safety measures (including conjunctival hypearemia) were detected. CONCLUSIONS AND RELEVANCE: Bimatoprost produced a statistically significant greater IOP reduction compared to tafluprost with minimal to no difference in side effects. This should be borne in mind when weighing up the pros and cons of preserved versus preservative-free prostaglandin analogue therapy. CLINICALTRIALS.GOV IDENTIFIER: NCT02471105.

Personalising surgical treatments for glaucoma patients.

Surgical treatments for glaucoma have relied for decades on traditional filtering surgery such as trabeculectomy and, in more challenging cases, tubes. Antifibrotics were introduced to improve surgical success in patients at increased risk of failure but have been shown to be linked to a greater incidence of complications, some being potentially vision-threatening. As our understanding of glaucoma and its early diagnosis have improved, a more individualised management has been suggested. Recently the term "precision medicine" has emerged as a new concept of an individualised approach to disease management incorporating a wide range of individual data in the choice of therapeutic modalities. For glaucoma surgery, this involves evaluation of the right timing, individual risk factors, targeting the correct anatomical and functional outflow pathways and appropriate prevention of scarring. As a consequence, there is an obvious need for better knowledge of anatomical and functional pathways and for more individualised surgical approaches with new, less invasive and safer techniques allowing for earlier intervention. With the recent advent of minimally invasive glaucoma surgery (MIGS) a large number of novel devices have been introduced targeting potential new sites of the outflow pathway for lowering intraocular pressure (IOP). Their popularity is growing in view of the relative surgical simplicity and apparent lack of serious side effects. However, these new surgical techniques are still in an era of early experiences, short follow-up and lack of evidence of their superiority in safety and cost-effectiveness over the traditional methods. Each year several new devices are introduced while others are withdrawn from the market. Glaucoma continues to be the primary cause of irreversible blindness worldwide and access to safe and efficacious treatment is a serious problem, particularly in the emerging world where the burden of glaucoma-related blindness is important and concerning. Early diagnosis, individualised treatment and, very importantly, safe surgical management should be the hallmarks of glaucoma treatment. However, there is still need for a better understanding of the disease, its onset and progression, the functional and structural elements of the outflow pathways in relation to the new devices as well as their long-term IOP-lowering efficacy and safety. This review discusses current knowledge and the future need for personalised glaucoma surgery.

Combination of snapshot hyperspectral retinal imaging and optical coherence tomography to identify Alzheimer's disease patients.

INTRODUCTION: The eye offers potential for the diagnosis of Alzheimer's disease (AD) with retinal imaging techniques being explored to quantify amyloid accumulation and aspects of neurodegeneration. To assess these changes, this proof-of-concept study combined hyperspectral imaging and optical coherence tomography to build a classification model to differentiate between AD patients and controls. METHODS: In a memory clinic setting, patients with a diagnosis of clinically probable AD (n = 10) or biomarker-proven AD (n = 7) and controls (n = 22) underwent non-invasive retinal imaging with an easy-to-use hyperspectral snapshot camera that collects information from 16 spectral bands (460-620 nm, 10-nm bandwidth) in one capture. The individuals were also imaged using optical coherence tomography for assessing retinal nerve fiber layer thickness (RNFL). Dedicated image preprocessing analysis was followed by machine learning to discriminate between both groups. RESULTS: Hyperspectral data and retinal nerve fiber layer thickness data were used in a linear discriminant classification model to discriminate between AD patients and controls. Nested leave-one-out cross-validation resulted in a fair accuracy, providing an area under the receiver operating characteristic curve of 0.74 (95% confidence interval [0.60-0.89]). Inner loop results showed that the inclusion of the RNFL features resulted in an improvement of the area under the receiver operating characteristic curve: for the most informative region assessed, the average area under the receiver operating characteristic curve was 0.70 (95% confidence interval [0.55, 0.86]) and 0.79 (95% confidence interval [0.65, 0.93]), respectively. The robust statistics used in this study reduces the risk of overfitting and partly compensates for the limited sample size. CONCLUSIONS: This study in a memory-clinic-based cohort supports the potential of hyperspectral imaging and suggests an added value of combining retinal imaging modalities. Standardization and longitudinal data on fully amyloid-phenotyped cohorts are required to elucidate the relationship between retinal structure and cognitive function and to evaluate the robustness of the classification model.

Procedural aspects of the organization of the comprehensive European Board of Ophthalmology Diploma examination.

The comprehensive European Board of Ophthalmology Diploma (EBOD) examination is one of 38 European medical specialty examinations. This review aims at disclosing the specific procedures and content of the EBOD examination. It is a descriptive study summarizing the present organization of the EBOD examination. It is the 3rd largest European postgraduate medical assessment after anaesthesiology and cardiology. The master language is English for the Part 1 written test (knowledge test with 52 modified type X multiple-choice questions) (in the past the written test was also available in French and German). Ophthalmology training of minimum 4 years in a full or associated European Union of Medical Specialists (UEMS) member state is a prerequisite. Problem-solving skills are tested in the Part 2 oral assessment, which is a viva of 4 subjects conducted in English with support for native language whenever feasible. The comprehensive EBOD examination is one of the leading examinations organized by UEMS European Boards or Specialist Sections from the point of number of examinees, item banking, and item contents.

Comparison of preservative-free latanoprost and preservative-free bimatoprost in a multicenter, randomized, investigator-masked cross-over clinical trial, the SPORT trial.

PURPOSE: The aim of this study was to investigate the efficacy and safety of Bimatoprost Unit Dose Preservative Free (BUDPF) and Latanoprost Unit Dose Preservative Free (LUDPF). METHODS: A prospective, randomized, investigator-masked, cross-over comparison was used. Inclusion criteria were ocular hypertension (OHT) or open-angle glaucoma (OAG) with a maximum intraocular pressure (IOP) of 21 mmHg on a preserved prostaglandin monotherapy. After 6 weeks washout, patients were randomized to BUDPF or LUDPF for 3 months and then switched to the other treatment for 3 months. IOP curves were performed at baseline and after each treatment period. Statistical analysis was performed in a R programming environment. Linear mixed modeling was used to account for repeated measures on the same subject and clustering of observations from the same center. Safety outcomes included visual acuity, adverse events, slit-lamp biomicroscopy, ocular tolerability, and optic nerve assessment. RESULTS: Analysis at 6 months (primary outcome) showed a 1.6 ± 0.5-mmHg difference in IOP values between LUDPF and BUDPF (p < 0.01). A mean intra-subject IOP difference of 0.9 ± 0.2 mmHg (LUDPF - BUDPF) was observed (p < 0.01).. Significant differences in IOP were observed for both drugs at 3 and at 6 months compared to baseline: -4,0 ± 0.5 mmHg for both BUDPF and LUDPF at 3 months (p < 0.01 for both drugs; p = 0.32 between the two drugs); -5.2 ± 0.5 and -3.4 ± 0.5 mmHg for BUDPF and LUDPF, respectively (both p < 0.01), at 6 months. Both drugs were tolerated well, the only statistically significant difference being lower hyperemia scores for LUDPF (albeit low for both drugs). CONCLUSIONS: This study demonstrates a superior efficacy of BUDPF over LUDPF in lowering IOP. The results are consistent both in the parallel comparison between the two treatment groups at 6 months as well as in the intra-subject pressure comparison.

[Arterial hypertension and glaucoma: watch out for nocturnal blood pressure]. / Pression artérielle et glaucome : attention à la pression artérielle nocturne.

Glaucoma is the second cause of blindness in industrialized countries. One of the principal risk factors for open angle glaucoma, the most prevalent form of the disease, is an increase in intraocular pressure (IOP). An excessive drop in nocturnal blood pressure (so called dipping) can be harmful by increasing ischemic damage to the optic nerve. In case of progression of glaucoma despite well controlled IOP, 24h BP monitoring is recommended. The relationship between IOP and systemic blood pressure has been the subject of several studies that are reviewed in this article. The influence of antihypertensive drugs on IOP is also discussed.

Le glaucome est la 2e cause de cécité dans les pays industrialisés. Un des principaux facteurs de risque du glaucome à angle ouvert, la forme la plus fréquente, est l'augmentation de la pression intraoculaire (PIO). Une baisse excessive de la pression artérielle (PA) pendant la nuit (dipping) favorise des processus ischémiques au niveau du nerf optique, qui jouent un rôle dans la progression du glaucome chez certains patients. En cas d'une progression du glaucome malgré une PIO satisfaisante, la mesure de la PA de 24 h est recommandée pour détecter l'hypotension nocturne. La relation entre la PIO et la pression artérielle systémique reste controversée, et est passée en revue dans cet article, tout comme les recherches ayant observé l'effet des différentes classes d'hypotenseurs sur la PIO.

Introduction of subspecialty examinations by the European Board of Ophthalmology (EBO) in close collaboration with European Subspecialty Ophthalmological Societies: FEBO-SA.

The European Board of Ophthalmology (EBO) aims to establish common European standards in ophthalmology. The comprehensive EBO Diploma (EBOD) examination has been officially used since 1995 by an increasing number of European countries to assess the level of education in ophthalmology of their residents at the end of their training. The current comprehensive EBOD examination ensures a minimum standard of knowledge. We present an update on the EBO plans to establish a subspecialty advanced EBOD (AdEBOD) examination in order to award ophthalmologists who complete subspecialty training with formal recognition of their expertise. The purpose, structure and process of the AdEBOD examination are presented.

Preservative-free treatment in glaucoma: who, when, and why.

PURPOSE: To review and summarize the available literature on the effect of preservatives on the eye, to provide practical guidance for the clinical assessment of the ocular surface in glaucoma patients, and to define patient populations that might benefit from preservative-free topical intraocular pressure (IOP)-lowering agents. METHODS: This manuscript is based on a combination of a literature review on preservatives and the eye and expert opinion from glaucoma specialists with an interest in ocular surface disease. RESULTS: There is an increasingly recognized association between eyedrop preservatives and ocular surface disease. Preservative-free therapy is now available for a wide range of active compounds, although there are still some misconceptions regarding their appropriate use. For patients treated topically for glaucoma or ocular hypertension, a rough estimate could be that 20% may need treatment with topical IOP-reducing agents that are free from preservatives. CONCLUSION: This review provides an up-to-date account of the literature regarding preservatives and the eye, as well as suggestions and recommendations on to when to use preservative-free antiglaucoma treatment.

The effect of learning curve on the surgical outcome of viscocanalostomy.

PURPOSE: To evaluate the influence of learning curve on the surgical outcome of viscocanalostomy. METHODS: Retrospective, interventional study. Chart review of the first consecutive open-angle glaucoma cases that received viscocanalostomy in 1 institution between July 1996 and June 2000. Overall success was defined as no visual field deterioration; postoperative intraocular pressure (IOP) ≤20 mm Hg; and IOP reduction ≥30% compared with baseline values with or without medication. When medications were not required, success was defined as complete. Demographic, procedural, and postoperative data were tabulated and analyzed. PRIMARY OUTCOME MEASURES: overall and complete success rates. SECONDARY OUTCOME MEASURES: number of glaucoma medications and surgical complications. RESULTS: A total of 180 cases were analyzed. Mean follow-up (±SD) was 28.9±5.9 months (range, 12-36 mo). Overall success has significantly improved from 64% to 91% when comparing the first 45 to the last 45 cases of the series (Mantel-Cox, P=0.005). Similarly, complete success has significantly improved from 38% to 73% (Mantel-Cox, P=0.004). The mean number of glaucoma medication (±SD) significantly decreased from 2.58±0.94 before surgery to 0.53±0.79 after surgery (Wilcoxon, P<0.001). Surgical complications decreased from 16 in the first 45 cases to 10 in the last 45 cases without reaching statistical significance (Pearson χ, P=0.315). CONCLUSIONS: Viscocanalostomy appears to safely reduce IOP in cases with medically uncontrolled open-angle glaucoma. Mastering viscocanalostomy procedure is achievable after the first 40 cases.

Renal sodium handling in patients with normal pressure glaucoma.

Low BP (blood pressure) is a recognized risk factor for some patients with NPG (normal pressure glaucoma). We have shown previously that patients with orthostasis have impaired circadian renal handling of sodium, which may contribute to the low BP. Therefore the aim of the present study was to examine the renal handling of sodium, the circadian variations in BP and the neurohormonal response to an orthostatic test in a selected subpopulation of 18 patients with NPG with vasospastic and orthostatic symptoms, and in 24 healthy control subjects. The variations in BP and renal tubular sodium handling were evaluated using 24 h ambulatory BP recordings, 24 h urine collections and determination of endogenous lithium clearance as a marker of proximal sodium reabsorption. The neurohormonal and BP responses to changes in posture were also determined in a 30 min orthostatic test. This selected group of patients with NPG had lower 24 h ambulatory BPs (P<0.001), and a more pronounced fall in BP when assuming an upright position (P<0.001) compared with controls. FE(Li) (fractional excretion of lithium) was higher in patients with NPG than controls during the day (36.6+/-21.8 compared with 20.4+/-8.7% respectively; P<0.01; values are means+/-S.D.) as well as during the night (38.8+/-41.9 compared with 19.7+/-10.8% respectively; P<0.02), suggesting a reduced reabsorption of sodium in the proximal tubule. This was compensated for by an increased distal reabsorption of sodium in patients with NPG (P<0.01). These data demonstrate that patients with vasospastic NPG have a high excretion of lithium, suggesting reduced sodium reabsorption in the proximal tubule, in spite of a low BP. The abnormal renal sodium handling might contribute to the maintenance of arterial hypotension and progression of the optic nerve damage in these patients.

Phacoviscocanalostomy for open-angle glaucoma with concomitant age-related cataract.

PURPOSE: To evaluate the efficacy and safety of combined viscocanalostomy and phacoemulsification (phacoviscocanalostomy) for medically uncontrolled open-angle glaucoma (OAG) with concomitant age-related cataract. DESIGN: Prospective, noncomparative, interventional case-series study. METHODS: Phacoviscocanalostomy was performed on 50 eyes of 50 consecutive patients with medically uncontrolled OAG and clinically significant age-related cataract. Surgical outcome was defined as an overall success by the following criteria: no visual field deterioration; no optic-neuropathy progression; postoperative intraocular pressure (IOP) /= 30% compared to baseline values with or without medication. When medications were not required, success was defined as complete. The surgical outcome and the complication rates were documented and analyzed up to 36 months postoperatively. RESULTS: Mean follow-up (+/-SD) was 29.02 +/- 7.09 months. Mean, baseline IOP (+/-SD) had significantly decreased from 23.51 +/- 4.48 mmHg to 14.06 +/- 1.64 mmHg at the last follow-up visit for each patient (p < 0.001). The overall success was 94% at 12 months, 92% at 24 months, and 82% at 36 months. The success was complete in 74% at 12 months, and in 67% at 24 months and at 36 months. No serious complications were documented. CONCLUSION: Phacoviscocanalostomy can be considered an efficient and safe alternative surgical modality for medically uncontrolled OAG with concomitant age-related cataract.

Primary viscocanalostomy for juvenile open-angle glaucoma.

PURPOSE: To evaluate the efficacy and safety of primary viscocanalostomy for medically uncontrolled juvenile open-angle glaucoma (JOAG). DESIGN: Prospective, noncomparative, interventional case-series study. METHODS: The study included 20 eyes of 20 consecutive patients with medically uncontrolled JOAG who were treated by viscocanalostomy at one institution. No surgical or laser procedure preceded viscocanalostomy. Surgical outcome was defined as an overall success by the following criteria: no visual field deterioration, no optic-neuropathy progression, postoperative intraocular pressure IOP < or =20 mm Hg, and IOP reduction > or =30% compared with baseline values with or without medication. When medications were not required, success was defined as complete. Cases that did not fulfill the aforementioned criteria and cases in which a surgical revision or further goniopuncture was performed were defined as a failure. RESULTS: Gender distribution was similar. Fourteen eyes belonged to the white race; five eyes belonged to the black race, and one eye belonged to Arab ethnicity. Mean age (+/-SD) at operation was 33.77 +/- 6.16 years, with the mean preoperative IOP (+/-SD) at 22.9 +/- 4.77 mm Hg. Thirty-six months after operation, 16 cases (80%) were considered an overall success. In 11 cases (55%), success was complete. Four cases (20%) were considered failures. No serious complications were documented either during or after operation. In two cases (10%), we documented a spontaneously reabsorbed microhyphema. Trabeculo-Descemet-membrane microperforation occurred in two cases (10%). In two other cases (10%), Trabeculo-Descemet-membrane perforation occurred and was accompanied by iris prolapse that needed peripheral iridectomy. CONCLUSION: Primary viscocanalostomy can efficiently and safely reduce intraocular pressure in cases of medically uncontrolled JOAG and provide a rational alternative to conventional surgical modalities.