Lietuvos Sveikatos Mokslų Universitetas

Lietuvos Sveikatos Mokslų Universitetas

Lithuanian University of Health Sciences

Faculty of Medicine

Department of Ophthalmology

Title of Master’s Thesis:

Endoscopic Orbital Decompression, Outcomes and Impact

Author:

Gabriele Tvaskus

Prof. Jurate Jankauskiene MD, PhD

Kaunas

TABLE OF CONTENTS

Aims and Objectives………....8

Literature Review………...9 Methods...12 Results...13 Discussion...17 Conclusions...19 References...20

SUMMARY

Research title: Endoscopic orbital decompression, outcomes and impact

Aim: To provide an up to date literature review on endoscopic orbital decompression in

Graves ophthalmopathy, its complications and outcomes.

Objectives:

1. To identify effects of Grave’s ophthalmopathy. 2. To explore the impact of Grave’s ophthalmopathy

3. To analyze outcomes of various studies on endoscopic orbital decompression

Methodology: This was a review of the literature where the searches were conducted using

Medline (PubMed), Google Scholar and Science direct. Key words such as “Grave’s ophthalmopathy”, “orbital decompression” “endoscopic” were combined. 55 studies were identified. The studies which analyzed a combined approach to orbital decompression or were excluded. Studies which, within the last 10 years, analyzed ten or more endoscopic trans nasal orbital decompressions were selected. There were no geographical exclusions.

Results: 10 articles were identified which fit the selection criteria. The studies evaluated a

total of 570 performed endoscopic orbital decompressions for various indications. All studies measured the decrease of proptosis which ranged from a mean decrease of 2.07 mm (1) to 8.2 mm (2). 6 studies reported the Hertel values before and after the endoscopic orbital decompression. The range of values before the orbital decompression were 20.1 mm (1,3) to 24.7 mm (4). After the orbital decompression the range of Hertel values was 17.9 mm (3) to 19 mm (4–7) . Visual field defects were taken into account in 3 articles (3,6,8). 8 studies reported overall improved visual acuity. 8 articles reported on diplopia with variations of preexisting diplopia being unchanged, preexisting diplopia resolving and new onset diplopia emerging. The most common complication aside from diplopia, was post endoscopic orbital decompression epistaxis, occurring in 19 patients. (2) Other common complications were

intraoperative bleeding, hematoma and sinusitis. The most severe complication was 1 incidence of cerebrospinal fluid leak which required surgery to be performed again. (1)

Conclusion: Endoscopic orbital decompression seems to decrease proptosis and improve

visual acuity rendering it a safe and effective method of orbital decompression. Graves

ophthalmopathy greatly diminishes the quality of life in those afflicted by it. Endoscopic orbital decompression offers a method to decrease the symptoms and signs caused Graves

ophthalmopathy, therefore improving quality of life. Confirming the best techniques in treating Graves ophthalmopathy is difficult due to the variability of the disease and lack of studies performed.

ACKNOWLEDGEMENTS

Thank you to Prof. Jankauskiene for her support throughout this process, her vast knowledge of this field was a substantial part of this thesis.

CONFLICT OF INTEREST

The author discloses no conflicts of interest pertaining to this study.

ABBREVIATIONS

Graves Ophthalmopathy (GO)

Endoscopic Orbital decompression (EOD) Randomized Controlled Trial (RCT)

Quality of Life (QOL)

INTRODUCTION

Graves ophthalmopathy (GO) is an autoimmune disorder affecting the majority of patients afflicted with Graves disease. GO manifests by causing inflammation and expansion of the orbital fat and extraocular muscles. (9) These changes in the eye lead to clinical features such as proptosis, eyelid retraction, restrictive myopathy, exposure keratitis and compressive optic neuropathy. (5)

GO is mainly treated with corticosteroids, retrobulbar radiotherapy and orbital decompression. (5) Indications for orbital decompression are vision threatening conditions such as optic neuropathy and severe proptosis with exposure keratitis. Orbital

decompression can also be used to treat the disfiguring appearance caused by proptosis. Various methods of orbital decompression exist and the approach chosen depends on the manifestation of the disease. (6)

GO is extremely debilitating so effective treatment with endoscopic orbital

decompression (EOD) is very important. Although there are treatment guidelines available for GO, each patient is looked at individually and there is no specific EOD technique which is proven the most beneficial. There are few randomized controlled trials (RCTs) within heterogeneous populations and those which are available, differ in treatment outcome measures. (3)

Due to the fact that orbital decompression is performed on a case by case basis, the aim of this thesis is to review the scientific studies available on EOD and to describe the outcomes and complications in order to improve understanding of the procedure.

AIMS AND OBJECTIVES

Aim: To provide an up to date literature review on endoscopic orbital decompression in

Graves ophthalmopathy, its complications and outcomes.

Objectives:

1. To identify effects of Grave’s ophthalmopathy. 2. To explore the impact of Grave’s ophthalmopathy.

3. To analyze outcomes of various studies on endoscopic orbital decompression.

LITERATURE REVIEW

Effect of Graves ophthalmopathy on the eye

Despite the fact that there is not full understanding of the pathophysiology of GO, Zoumalan et al. explains that there is an active and inactive phase of the disease. The active phase, which generally lasts 6 months to 3 years, results from lymphocytes infiltrating the orbital and periorbital fat and muscles. It is difficult to predict the course of the active phase due to the great variability in length and severity among individuals. Once the active

inflammatory process subsides, this marks the beginning of the latent inactive phase which is characterized by fibrosis.(9) All these inflammatory and fibrotic changes result in the

expansion of the extraocular muscles, retrobulbar fat and connective tissue causing a multitude of signs and symptoms affecting vision and appearance. (10)

Jankauskiene et al. (6) described the effect of thyroid pathology and exophthalmos on visual acuity and refraction. Data of 105 individuals (10 men and 95 women) with a mean age of 49±4.5 years all suffering from thyroid pathology was compared to the data of 23 healthy individuals of a similar age. Those individuals with thyroid pathology had a visual acuity of 0.71±0.035 in the right eye, and 0.73±0.045 in the left eye. The visual acuity in the control group was 0.89±0.06, P<0.05 in the right eye and 0.92±0.07, P<0.05 in the left eye, showing that visual acuity was significantly worse in those with thyroid pathology. It was also it was seen that visual acuity was worse in those individuals with exophthalmos being greater than or equal to 17 mm compared to the control group. (11)

Jankauskiene et al. performed a similar study assessing visual acuity, proptosis and refraction in different age groups. Data of 49 individuals with a mean age of 43.2±3.8 years all suffering from Graves disease was compared to the data of 35 healthy individuals of a similar age. The visual acuity of those individuals with Graves disease was 0.7±0.16. the visual acuity in the control group was 0.9±0.1 (P=0.001), showing that visual acuity was significantly worse in those individuals with thyroid pathology. (12)

In the same study Hertel exophthalmometric values were compared between the two groups. The adults with Graves disease had a mean Hertel value of 18.05±2.91 mm, ranging from 13.5 to 23.0 mm. This was significantly higher than the Hertel values of the control group which had a mean of 15.27±1.23 mm, ranging from 13.0 to 17.5 mm. (12)

Decreasing visual acuity and advancement of exophthalmos in these individuals demonstrate a great change to the functional quality of the eye as well as the cosmetic

appearance. The ability to do daily tasks such as reading and working may diminish and the change in outward appearance may have a very negative effect on emotional wellbeing.

Effect of Graves ophthalmopathy on quality of life

Wickwar et al. states “People with GO have been found to have a poorer quality of life than patients with other chronic conditions including diabetes, emphysema, and heart failure.” (13) This statement highlights the harsh effect GO has on the quality of life (QOL) of those affected by it.

Delfino et al. studied the correlation of GO QOL scores with disease severity and activity. 41 individuals with GO were compare to a control group made up of 15 individuals without GO. Results showed that a significant difference in functional and appearance QOL exists between those affected with GO and those without. A negative correlation was seen between the severity of the GO and both the functional and appearance QOL in those surveyed. (14)

In contrast, the study which Wickwar et al. performed found that among the 121 individuals with GO surveyed, the functional QOL score was comparable to the normative values of a previous GO sample, but the GO-QOL appearance scores were significantly lower. This prompted the idea that the aesthetic effects of GO are having an even greater impact on the patients than previous literature had reported. (13)

These studies shed light on the immense importance of GO treatment which would minimize these signs and symptoms negatively affecting patients’ QOL. The 2016 European Thyroid Association/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy recommendation is to have a patient focused approach in treating GO and keeping in mind the effects the disease and treatment have on the patients’ QOL. (15) Although there is not one treatment which suits all patients with GO, EOD does prove to have beneficial effects on QOL in those individuals which have indications for it.

A long-term longitudinal study performed by Iacobaeus et al. confirmed the positive long-term effect of EOD on QOL. 76% of patients reported an improvement of 10 or more points in their QOL scores, deeming the increase clinically significant. Most patients were satisfied with their surgical result and even when the patients were divided into subgroups dependent on the indication for the EOD, the functional and appearance QOL improvements were significant. (16)

Predictability in orbital decompression outcomes

The significant improvement in QOL of patients with severe GO after EOD demonstrates the need for more studies of EOD to be done to find the most optimal technique. Currently there are many methods to perform EOD and the method chosen usually depends on the experience of the surgeon rather than objective criteria. The anatomical characteristics of each patients orbit makes it difficult to pin point the rate of exophthalmos reduction that will be achieved with any chosen surgical technique.

Borumandi et al. explains that there is a lack of predictability when it comes to orbital decompression. He speculates that the variability of orbital morphology in GO plays a role in the varied outcome of EOD even when using the same technique. There is also a lack of information in the studies detailing surgeons’ aims and prospective outcome measures for the various surgical techniques. Through this study Borumandi et al. calls for the need of clinical trials to improve predictability in the outcomes of EOD and potentially form individualized anatomy based surgical concepts for performing EOD. (17)

METHODS

This was a review of the literature to identify articles referencing Graves

ophthalmopathy, endoscopy and orbital decompression. The searches were conducted using Medline (PubMed), Google Scholar and Science direct. Search terms such as “Grave’s ophthalmopathy”, “thyroid eye disease”, “orbital decompression”, and “endoscopic” were used. Studies were limited to those done in the last 20 years (1999-2019) due to the

advancement in surgical techniques, older studies become less relevant. A total of 55 articles were identified in the search. The studies which analyzed a combined approach to orbital decompression were excluded. Those studies which analyzed 10 or more endoscopic orbital decompressions were selected. There were no geographical exclusions. After finding eligible titles and abstracts, full articles were obtained and examined to determine their relevance. The studies were not reviewed for quality assessment.

RESULTS

After performing the search,10 articles were identified which fit the selection criteria. The data extracted from these studies can be seen in Table 1. All studies found were retrospective studies, which have their limitations. The studies evaluated a total of 570

performed EODs for various indications. Malik et al. reviewed only cases where the indication for EOD was mainly cosmetic. (7) The outcomes were observed in the varied time frame of 1 week to 166 months after EOD depending on the study. All studies measured the decrease of proptosis which ranged from a mean decrease of 2.07 mm (1) to 8.2 mm (2). 6 studies

reported the Hertel values before and after the EOD. The range of values before EOD was 20.1 mm (1,3) to 24.7 mm (4). After EOD the range of Hertel values was 17.9 mm (3) to 19 mm (4–7) . Visual field defects were taken into account in 3 articles (3,6,8). Wu et al. (2) and Lal et al. (18) did not report on visual acuity changes for all of their patients but in the

remaining 8 studies visual acuity improved overall. 8 articles reported on diplopia with variations of preexisting diplopia being unchanged, preexisting diplopia resolving and new onset diplopia emerging. 48 patients had transient new onset diplopia, 5 patients had

preexisting diplopia which resolved after EOD and 49 patients had new onset diplopia with no reported resolution. The most common complication aside from diplopia, was post EOD epistaxis, occurring in 19 patients. (2) Other common complications were intraoperative bleeding, hematoma and sinusitis. The most severe complications were 1 incidence of cerebrospinal fluid leak which required surgical reexploration (1) and 3 new cases of esotropia. (19)

Table 1. Summary of endonasal orbital decompression studies identified in this review Research article first author, year Number of Orbits Change in

proptosis Hertel Mean value Visual field defects Intraocular pressure Decrease Effect on

visual acuity Effect on diplopia Complications

Stiglmayer et al. 2004 (4) 32 4.6 ± 1.7 (p<0.001), ranging from 2-8 mm Pre EOD: 24.7 ± 2.4 mm Post EOD: 19.0 ± 2.6 mm Not

reported Decreased by a mean of 3.4 ± 3.0 mmHg from pre EOD: 19.4 ± 3.4 to 16.2 ± 3.0 mmHg post EOD Improved from pre EOD 0.81±0.28 (mean ±SD) to post EOD 0.92± 0.21 (p=0.0032) 11 cases pre-existed, 2 resolved and in 9 persisted, new-onset diplopia in 8 patients Deterioration of ocular motility disturbance (18 eyes), slight intraoperative bleeding (3 patients), post EOD periorbital hematoma (1 patient) Malik et al. 2008 (7) 20 Mean decrease of 3.7 ± 2.2 mm (t= 6.5, p< 0.001) Pre EOD: 22.7 ± 4.5 mm, post EOD: 19.0 ± 4.0 mm Not reported Not reported Improved after both 3 months and 1 year 1 patient with diplopia that resolved, 7 with preexisting diplopia with no change, 4 had new onset, 3 of those had bilateral EOD, 1 new onset unilateral EOD which resolved in 20 months 1 patient with acute sinusitis, 1 patient with post EOD rhinorrhea, 2 patients with epiphora She et al. 2012 (1) 42 1-month post EOD: 1.93 ± 0.25 mm, range 0.5 to 0.6 mm (p < 0.01) 3 months post EOD: 2.07 ± 0.30 mm range 0-7 mm (p < 0.01) Pre EOD: 20.10 ± 3.61 mm, 1-month post EOD: 18.17 ± 3.16 mm 3 months post OD: 18.02 ± 3.06 mm Not reported 1-month post EOD: 4.40 ± 0.72 mmHg, 3 months post EOD: 4.38 ± 0.80 mmHg Increased from 0.45 ± 0.34 to 0.66 ± 0.36 and 0.70 ± 0.35 at 1- and 3-months post EOD. Vision improved for all patients except 1 which reduced, 1 patient had decompression for a blind eye

20 patients, 35 orbits with preexisting , all persisted post EOD, 1 patient 2 orbits with new onset 1 CSF leak Vukovic et al. 2012 (5) 97 Decreased from 2-8 mm in all orbits Pre EOD: 23.7 ±2.4 mm, post EOD: 19.0 ± 2.6 mm Not reported Pre EOD: 19.4 +_3.4 mmHg, post EOD: 16.2 +_3.0 mmHg Increased from 0.81 +_0.28 to 0.92 +_0.21 23 patients with new onset diplopia, diplopia persisted in 49 out of 53 patients, 3 patients had intraoperative bleeding; 2 patients had orbital hematoma

Research article first author, year Number of orbits Change in proptosis Mean Hertel value Visual field defects Intraocular pressure decrease Effect on visual acuity Effect on diplopia Complications Lal et al. 2013 (18) 24 Mean decrease of 3.70 mm, range of 2-6 mm Not reported Not reported Not reported Significant improvement of the eye with partial visual loss, but no improvement in the eye with complete visual loss. New onset invariable in all cases, resolved in 2-8 weeks Persistent frontal sinusitis for 1 month in 1 patient Gulati et al. 2015 (6) 66 Mean decrease of 4.0 mm Pre EOD: 22.5 mm (14-29 mm), post EOD: 19 mm (11-26 mm) Visual fields were normal in 16 patients, smaller defects in 4 patients and larger defects in 4 patients Decrease from 18 mmHg (10-27mmHg) to 14 mmHg (8-24 mmHg) Improved by more than 1 line in 14 eyes, unchanged in 48, worsened by more than one line in 3 eyes, median pre EOD best corrected visual acuity was 0.8(0.05-1.25) and at follow up was 1.0(0.4-1.25) 17 patients with preexisting diplopia, 7 with new onset, 8 with worsening 3 patients with delayed sinusitis post EOD Wu et al. 2015 (2) 216 Mean decrease of 8.2 ± 1.8 mm range 4-11 mm Not

reported Not reported Not reported Not reported 25 cases (23.1%) of new-onset diplopia with complete resolution in 23 of these within 3 months, 2 patients required squint surgery 19 patients with post EOD epistaxis, 2 patients with intra orbital hemorrhages 1-day post EOD, 3 patients with orbital emphysema within 5 days post EOD Seibel et al. 2016 (3) 12 Not

reported Pre EOD: 20.10 ± 4.1 mm, 1-week post EOD: 19.2 ± 4.6 mm, 3 months post EOD: 18.8 ± 4.4 mm, 1-year post EOD: 17.9 ± 4.7 mm Pre EOD: 2.7 ± 4.0, 1-week post EOD: 0.8 ± 2.6, 3 months post EOD: -0.1 ± 2.3, 1-year post EOD: 0.3 ± 3.0 In primary gaze - Pre EOD: 15.0 ± 4.7mmHg, 1-week post EOD: 15.4 ± 3.6 mmHg, 3 months post EOD: 15.9 ± 2.6, 1-year post OD: 15.4 ±3.3 mmHg Pre EOD: 0.68 ± 0.22, 1-week post EOD: 0.74 ± 0.16, 3 months post EOD: 0.87 ± 0.12, 1-year post EOD: 0.77 ± 0.12 Pre EOD: 5 patients with diplopia, post EOD: 3 patients with diplopia None reported

Research article first author, year Number of orbits Change in proptosis Mean Hertel value Visual field defects Intraocular pressure decrease Effect on visual acuity Effect on diplopia Complications El-Samkary et al. 2017 (8) 18 Mean decrease of 3.61 ± 0.18 mm, 77.78% cases of proptosis have resolved, 2 cases with residual proptosis Not

reported Pre EOD: 12 cases with mild, 4 with moderat e, 1-month post EOD 15 with no defect, 3 with mild defects Not

reported Mean change of 1.39 lines improvement

None

reported None reported

Park et al. 2019 (19) 43 Mean decrease of 2.99 ± 0.96 mm at 3 months post EOD, 3.07 ± 1.24 mm after 1 year Not

reported Not reported Pre EOD: 15.32 ± 2.94 mmHg, 3 months post OD: 14.60 ± 2.54 mmHg, 1-year post OD: 14.51 ± 2.68 Improved after both 3 months and 1 year None

reported 3 patients with new onset esotropia

DISCUSSION

This study investigated the outcomes of EOD in patients with GO. Ting et al. explains that when comparing EOD to an open approach, EOD allows for enhanced visualization of key anatomical landmarks, a lower complication rate, and avoidance of external facial incisions and scar.” (20) This makes the endoscopic method very advantageous when choosing an approach to orbital decompression.

This study did show improvement in proptosis and visual acuity in the majority of cases indicating that this is an effective treatment option for GO. Ting et al. reports new onset or worsening diplopia being the most common complication of EOD, occurring in 15-63% of patients. (20) This study showed 18.4% occurrence of new onset or worsening diplopia amongst all cases. There were various complications associated with the EOD but the most severe, a cerebrospinal fluid leak only occurred in one patient and only 3 cases of esotropia developed. The other complications were relatively minimal such as slight intraoperative bleeding and sinusitis. These finding indicate that EOD is a relatively safe procedure.

Even though the endoscopic method was used throughout the studies, there was great variability in the outcomes of visual acuity and proptosis reduction. Assorted variables such as morphology of the orbits before EOD and indications for EOD could have possibly contributed to the varied range of outcomes.

It is necessary to consider the individual anatomy and morphology of all 570 orbits when comparing outcomes of EOD. Since GO affects the retrobulbar fat, connective tissue and extraocular muscles in various extents, each orbit has a different composition. This, combined with the severity of the inflammation and the size of the orbit influences the degree of proptosis had by the patient. In the cases investigated, Hertel values before EOD were in a range of 20.1 mm (1,3) to 24.7 mm (4). The higher or lower the Hertel value before EOD plays a part in the proptosis achievable with EOD.

Another factor possibly contributing to the variation is the varying indications included in the studies of EOD. Compressive optic neuropathy, corneal exposure and cosmetic

deformity all indicate the need for EOD. Lal et al. included patients with all indications for OD in his study, meanwhile, in the study done by Malik et al. the patients included had the main indication being cosmetic.

As Borumandi et al. observed in his study, the authors of these studies did not include predicted outcomes of the EOD which would have made it possible to evaluate the results of

the surgeries based on what was predicted. If they had it would have made a great

contribution to assessing outcomes of EOD techniques based on anatomy and morphology of the orbit. (17) It would be invaluable if future studies explored the peculiarities of the anatomy of each of the orbits being operated to hopefully in the future be able to provide more

standardized procedures for the surgical treatment of GO.

As was explained previously, outcomes of surgery greatly impact QOL and in a

disease which affects many parts of the body, improvements in treatment are always needed. EOD does improve both function and appearance but a more tailored approach might be beneficial in increasing that improvement. If more research was available documenting the anatomy and morphology of the orbits linked to the of type of surgery performed and its outcome, predicting outcomes of these surgeries would be more possible.

CONCLUSION

GO is a very complex disease affecting the patients in a functional and aesthetic way. It greatly diminishes the quality of life in those afflicted by it. EOD offers a method to

decrease the symptoms and signs caused Graves ophthalmopathy, therefore improving quality of life. Based on the studies evaluated, EOD seems to decrease proptosis and improve visual acuity rendering it a safe and effective method of orbital decompression. Confirming the best techniques in treating Graves ophthalmopathy is difficult due to the variability of the disease and lack of studies performed.

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