A Systematic Review Article on Orbital Exenteration: Indication, Complications and Reconstruction Methods

Abstract

Orbital Exenteration is a major surgical procedure that consists of the removal of the orbital bone, orbital fat, eyeball, and its contents including extraocular muscles. It is an extensive and morbid surgical procedure. Our aim is to systematically review the indications, complications and reconstruction methods utilised for orbital exenteration. An objective electronic database search was conducted in PUBMED Central, MeSH, NLM Catalog, Bookshelf, and PUBMED published in 20 years period from 1999 till 2019. A total of 29 articles were shortlisted for the present review. Most of the studies have eyelid and canthus as most common primary site of malignancy leading to orbital exenteration. Basal cell carcinoma and squamous cell carcinoma being most common pathology. Other intraocular pathology was Retinoblastoma and melanoma. There were various reconstruction methods used by different authors and Sino-orbital fistula was most commonly occurring in majority of studies. Inspite of being a morbid surgery, Orbital Exenteration had acceptable survival and good quality of life. The aggressive pathology that requires orbital exenteration worldwide is mostly periorbital skin, sinus, and intraocular malignancies. The morbidity of the procedure is high with many surgical complications. However, in properly selected patients it can give better outcomes and survival.

Introduction

The Eye is probably the most important vital organ in the human body which maintains the social and psychological response. However, some condition warrants its removal. Orbital exenteration is a major surgical procedure that consists of the removal of the orbital bone, orbital fat, eyeball, and its contents including extraocular muscles. [1, 2] It is a disfiguring procedure because of the removal of so much content off the face and it is reserved for the malignant diseases of the eye as far as possible to achieve a negative margin and prolong survival. Bartisch described orbital exenteration for the first time in 1583. [3] The procedure underwent many modifications after this and modern total orbital exenteration was done in the early twentieth century by Golovine. [4] Among the malignant indications of orbital exenteration, basal cell carcinoma of periorbital regions and eyelids is most common. In some series, it makes up to even 90% of total orbital exenteration worldwide.[5, 6] Squamous cell carcinoma and sebaceous cell carcinoma are the next common malignancies.[7–9] Although the region-wise and disease prevalence geographically the indications for orbital exenteration may vary but it is largely unchanged. Management of orbit needing exenteration requires extensive multidisciplinary coordination and team includes A surgeon, plastic surgeon, medical and radiation oncologist, radiologist, and psychotherapist.[10] Reconstruction of the primary site post-orbital exenteration is very important in terms of reducing the wound-related complications, adjuvant therapies, and cosmesis.[11] Reconstruction should have less wound-related complications so that adjuvant therapy is not delayed otherwise the whole purpose of the major surgery is defeated and patients suffer from the poor outcome in terms of survival. Various reconstructive methods are applied by different Surgeons but none have been proven better than the others. In this article, we are going to review the malignant indications for orbital exenteration and various reconstructive options used by different surgeons. We also aim to find out the complications and success of the procedure reported by different studies.

Material and Methods

The electronic database search was done in PUBMED Central, PUBMED, NLM Catalog, MeSH with keywords i.e. orbital exenteration, reconstruction, sebaceous cell carcinoma, and orbital tumor. A 20 years literature search was done between 1999 and 2019.

Inclusion and Exclusion Criteria

Articles written in English and studies conducted on humans were selected according to specific inclusion and exclusion criteria. The studies which included orbital exenteration for malignant tumors and reconstruction methods were selected. Studies that didn’t fulfill the inclusion criteria were considered ineligible and excluded. Detailed inclusion and exclusion criteria are listed in Table 1.

Table 1.

Detailed inclusion and exclusion criteria

Inclusion criteria	Exclusion criteria
1. Original article	1. Case reports, Review articles, and Meta-analysis
2. Studies published in English	2. Articles studied Orbital Exenteration only in Benign disease
3. Studies conducted on Humans	3. Articles not in English
4. Articles studied orbital exenteration on malignant tumors	4. Studies conducted on Non-Humans
5. Articles describing reconstruction post Exenteration

Study Selection

Above keywords were used in the NCBI databases and a total of 240 articles were searched (n = 240). Articles were shortlisted between 1999 and 2020 (n = 187). After removing duplicate articles (n = 28), remaining studies (n = 159) were selected for the next step. In the next step, articles not published in english and conducted on non-human subjects were excluded (n = 52) and an abstract of 107 articles was carefully considered for the next step (n = 107). Among these articles, according to inclusion and exclusion criteria, full texts of 29 articles were critically analyzed (n = 29) for the systematic review. Table 2 diagrammatically represents the study selection protocol from different databases by Prisma.

Table 2.

Study selection protocol by Prisma

Data Retrieval and Aims of the Study

Authors carefully studied the articles, noted the year of publication, number of cases, indications for orbital exenteration, and methods of reconstruction used post-exenteration. This review aims to find out the various malignant diseases which led to orbital exenteration and the reconstructive methods used worldwide. We also aim to find out the outcome of the procedure in terms of major surgical complications and so that we can conclude regarding the best method suitable for reconstruction.

Results

Twenty-nine full-text articles were evaluated properly by the authors and clinical details i.e. total no of patients who underwent orbital exenteration, mean/median age of the patient, sex distribution, pathology of patients, and complication of the procedure. The majority of the articles provided the reconstructive methods used.

Indication of Orbital Exenteration

Most of the articles provided details regarding the commonest primary site involved by the malignant tumor which led to the orbital exenteration. Malignancy involving the eyelids was the major cause of Orbital Exenteration in the majority of the study. [12, 15, 16, 21, 23, 26–28, 32, 34, 35] Conjunctival and intraocular malignancy were also the prime cause in some of the studies. [13, 14, 25, 33] The study done by Paridaens et al. exclusively included only conjunctival melanoma patients who underwent orbital exenteration. [22] The mean/median age of the study population was generally older and ranged in the 7th or 8th decade. However, studies involving ocular tumors in majority eg. Retinoblastoma tend to have younger mean age. [13, 20, 33] Details of the studies are given below in Table 3.

Table 3.

Studies showing age, indications, and pathology of orbital exenteration

Study	Total patients/Male/Female	Mean/Median age (years)	The major site of Disease (Number of patients)	Major pathology
Zhang et al. [12]	102/55/45	67.5	Eyelid-41 Conjunctiva-32 Orbit-20	Squamous cell carcinoma-36 Melanoma-28 Basal cell carcinoma-17 Sebaceous carcinoma-6
Kiratli et al. [13]	100/56/44	39.4	Intraocular-29 Eyelid-23	Retinoblastoma- 29 Squamous cell carcinoma-10 Basal cell carcinoma-9 Sebaceous carcinoma-2
Aryasit et al. [14]	39/21/18	62.9	Conjunctiva-13 Eyelid-12 Lacrimal gland-6	Squamous cell carcinoma-14 Sebaceous carcinoma-3 Basal cell carcinoma- 2
Kasaee et al. [15]	176/97/79	55.43	Eyelid-89 Globe-43 Orbit-26 Conjunctiva-11	Basal cell carcinoma- 49 Squamous cell carcinoma- 41 Retinoblastoma- 35 Adenoid cystic carcinoma- 13
Soysal [16]	68/33/35	66.56	Eyelid-42 Conjunctiva-20	Basal cell carcinoma- 26 Squamous cell carcinoma- 14 Sebaceous carcinoma- 2 (All among Eyelid)
Shields et al.[17]	56/23/33	68		Melanoma-36 Basal cell carcinoma-4 Squamous cell carcinoma-5 Sebaceous carcinoma-3
Roche et al.[18]	22/-	62	Medial Canthus-9 Sinus-5 Zygoma-5
Simon et al. [19]	34/10/24	67		Squamous cell carcinoma-9 Basal cell carcinoma-6 Melanoma-5 Sebaceous carcinoma-3
Ben et al. [20]	27/15/12	30		Retinoblastoma-9 Squamous cell carcinoma-5 Melanoma-2 Basal cell carcinoma-1
Gerring et al. [21]	49/38/11	70.3	Eyelid-58% Medial canthus-18% Brow skin-18%	Basal cell carcinoma-22 Squamous cell carcinoma-17 Sebaceous carcinoma-10
Paridaens et al. [22]	95/38/57	57.7	Conjunctiva	Melanoma-95 (100%)
Rahman et al. [23]	68/35/33	68.2	Eyelid-38 Orbit-18 Conjunctiva-3	Basal cell carcinoma-28 Melanoma-10 Sebaceous carcinoma-9 Squamous cell carcinoma-6
Croce et al. [24]	8/6/2	75		Basal cell carcinoma-4
Taylor et al. [25]	14/7/7	66	Conjunctiva-8 Ocular-5 Eyelid-1	Melanoma-9 Squamous cell carcinoma-2 Sebaceous carcinoma-1
Nassab et al. [26]	32/20/12	68	Eyelid-28% Canthus-28%	Basal cell carcinoma-17 Melanoma-6 Sebaceous carcinoma-4
Nemet et al. [27]	38/26/12	69.9	Eyelid-19 Ocular-12	Basal cell carcinoma-9 Squamous cell carcinoma-6 Sebaceous carcinoma-4
Nagendran et al. [28]	25/14/11	64	Eyelid-13 Choroid-4 Conjunctiva-2	Squamous cell carcinoma-7 Basal cell carcinoma-3 Choroidal melanoma-4
Kato et al. [29]	37/17/20	62.2		Squamous cell carcinoma-16 Basal cell carcinoma-10
Maria et al. [30]	26/19/7	65.5		Squamous cell carcinoma-18
Qussemyar et al. [31]	26/10/16	68	Canthus-10 Eyelid-5 Conjunctiva-3	Basal cell carcinoma-11 Squamous cell carcinoma-9 Melanoma-1
Maheshwari [32]	15/9/6	53.86	Eyelid-8	Sebaceous carcinoma-4 Basal cell carcinoma-3 Squamous cell carcinoma-1
Ali et al. [33]	119/80/39	48.9	Conjunctiva-49 Eyelid-28 Orbital-21	Sebaceous carcinoma (Eyelid)-20
Pushker et al. [34]	26/12/14	58.7	Eyelid-14 Ocular-9 Orbital-2	Squamous cell carcinoma-10 Sebaceous carcinoma-6 Melanoma-5 Basal cell carcinoma-2
Kaur et al. [35]	25/20/5		Eyelid-8 Orbital-6

Histopathology

Studies selected for this review have a heterogeneous patient population and the histology of the disease varies widely across the studies. There are some studies which state that the basal cell carcinoma was the most common histology. [15, 16, 21, 23, 24, 26, 27, 31] However, Squamous cell carcinoma was the majority in some of the studies. [12, 14, 19, 28, 29, 34] In the studies done by Ali et al. and Maheshwari Sebaceous carcinoma was a major histological variant among eyelid malignancies. [32, 33] Intraocular melanoma and Retinoblastoma were among the other common malignancies.

Reconstruction Methods

Every study had different reconstruction methods. The majority of the study utilized multiple ways of reconstruction that’s why it is difficult to compare them as to which method is better. However, there are some common trends. Leaving the socket open to granulate and split or full-thickness skin grafting seemed to be preferred by many authors.[13, 23, 25, 27] This was combined by prosthetic application in a later stage by some. Few oncology centers used temporalis muscle flap to the cavity of the socket and combined with or without skin grafting over it. [31, 32, 36] Apart from these many local myocutaneous flaps were used i.e. cervicofacial flaps, forehead flaps, scalp flap, and latissimus dorsi flap. There were different types of free flaps also utilized for reconstruction in many studies including the study by Roche et al., Pryor et al. and Lopez et al. who used free flaps exclusively. [12, 18, 21, 28, 37, 39, 40] Details of the reconstruction and major complications are given below in Table 4.

Table 4.

Details of reconstructive methods and major complications

Study	Reconstruction	Major Surgical Complications
Uyar et al. [36]	Temporalis muscle flap	Paralysis of Facial nerve-3 Sino-Orbital fistula-2
Gerring et al. [21]	Split skin grafting-36 Free flaps-9 Locoregional flaps-4 Temporal muscle fill-1 Temporoparietal fascia flap-1 Lower and upper eyelid flap-1	Not reported
Rahman et al. [23]	Left to granulate (43) and skin grafting (21)	Sino-orbital fistula-15 Failed SSG-4 Chronic discharge-1 CSF leak-1
Croce et al. [24]	Full-thickness skin graft-5 LD flap-2 PMMC flap-1 Combined both-1	None
Pryor et al. [37]	Vertical rectus abdominis free flap-11 Transverse rectus abdominis free flap-2	Flap failure-1
Taylor et al. [25]	Left open to granulate-7 Eyelid lining socket-4 Skin grafting-3	Sino-orbital fistula-10 Chronic infection-6 Hemorrhage/graft failure- 1 each
Nassab et al. [26]	Skin grafting-20 Forehead flap-8 Scalp flap-2 Cervicofacial flap-2	CSF leak-4 Graft failed-2
Nemet et al. [27]	Left to granulate-24 Dermis fat graft-11 Skin grafting-3	Hemorrhage-1 Non-healing granulation-1 Wound dehiscence-1
Nagendran et al. [28]	Skin grafting-10 Myocutaneous eyelid skin flap-6 Radial forearm free flap-2 Pericranial flap-1	Sino-orbital fistula-2 CSF leak-1 Graft failure-3
Zhang et al. [12]	Local Myocutaneous flaps-76 Skin grafting-12 Free flaps-2 Combined-16	Sino-orbital fistula-4
Kiratli et al. [13]	Left to granulate except 1 dermal fat graft	Visible lamina papyracea-19 CSF leak-1
Rodrigues et al. [38]	Lateral frontal flap	None
Maheshwari [32]	Temporal muscle fill	CSF leak-1 Sino-orbital fistula-1
Soysal [16]	Left to granulate and eyelid cover	Sino-orbital fistula-18 Hemorrhage-4
Roche et al. [18]	Free flaps	Flap loss-2 Sino-orbital fistula-1
Lopez et al. [39]	Free flaps	Complete Flap loss-2 Partial flap loss-1
Rabey et al. [40]	Cervicofacial rotation advancement flap-8 Free flaps-6	Dehiscence-1 Partial flap necrosis-1
Qussemyar et al. [31]	Temporal muscle flap	Partial necrosis of flap-3 Hematoma-1
Maria et al. [30]	Temporalis muscle fill with a skin graft

Major Complications of the Orbital Exenteration

Among the major surgical complications the occurrence of the Sino-orbital fistula is most reported. [12, 16, 23, 25, 28, 36] Graft failure and flap loss have also occurred however, the incidence was less. [18, 23, 26, 28, 37, 39] CSF leak was also encountered in few cases. [13, 23, 26, 28, 32] Only one study reported facial nerve paralysis in 3 patients [36] and another study had visible lamina papyracea in 19 patients during surgery as complication [13].

Margin Status and Survival

Orbital Exenteration is an extensive surgery and one expects to achieve a tumor-free margin however, the reported margin status doesn’t match with the expectations. Simon et al., Gerring et al., Kiratli et al. and Zhang et al. reported 11 (32%) patients, 11 (22%) patients, 53 (53%) patients, and 21 (20.5%) patients with positive margins respectively.[12, 13, 19, 21] Highest margin positivity was reported by Ben et al. he had 23 (82%) patients with a positive margin for tumor. [20] Survival was assessed by a few authors after completing adjuvant therapies. According to Kato et al. survival at 1, 2 and 3 years was 70, 66.1 and 58.3% respectively. [29] Maria et al. calculated 69.8 months as mean overall survival and 5 years overall survival was 62.3%. [30] Similarly, Roche et al. found out that 1 year survival was 91% and 5 years overall survival was 64%. [18] Indicators of poor survival were bone erosion, positive margins, additional resection beyond exenteration [21].

Quality of Life

Quality of life was assessed by a set of questionnaire and experiences of patients by Pryor et al. he found that all the patients were satisfied with the treatment and outcome. [37].

Discussion

Orbital exenteration is an extensive surgical procedure where the eye and its supportive soft tissues (Bulbous part and adnexal structures) are removed as a whole. The main indication of such a procedure is a malignancy which is invading the vital structure and orbital exenteration is required to achieve the tumor-free margin. Malignant pathology can be primary ocular or secondary to periorbital skin, lacrimal glands, or sinus involving the eye. Orbital exenteration can be either total or subtotal. Total orbital exenteration is when eyelids and orbital periosteum is also sacrificed and subtotal if done extraperiosteally and eyelids are spared. One or more orbital walls can also be resected together with supporting extra orbital tissues depending on the contiguous spread of the disease. [41] Some life-threatening infective pathology also can leads to orbital exenteration i.e. Mucormycosis.

This systematic review aimed to find out the malignant indications for orbital exenteration throughout the world. Due to different study populations, there is a lot of heterogeneity in data, but the majority of studies stated eyelid and canthus as the most common periorbital location from which malignancy led to orbital exenteration. According to literature Basal cell carcinoma is the most common eyelid malignancy and it occurs in the 6th and 7th decade. [42, 43] In our systematic review results are per available literature. Our review also includes studies having intraocular malignancies e.g. Retinoblastoma, understandably they have a younger diseased population compared to studies that had periorbital skin and sinus malignancies in the majority.

Another aim of this study was to assess the reconstruction methods utilized across the studies and complications of the procedure. We have found that there are a wide variety of methods were preferred by different surgeons. Some used free flaps exclusively whereas some used various vascularized flaps i.e. temporalis muscle flap, pericranial flap, cervicofacial flaps, etc. Many surgeons left the cavity open to granulate and grafted skin. The selection of any technique is based on the extent of the orbital defect, previous local radiation therapy, sparing of the lid, the requirement of a prosthesis, and adjuvant radiotherapy also. Leaving the cavity open for spontaneous granulation is an easy method that allows for early detection of recurrences. However, healing takes a longer time. Delayed healing may reduce survival by further delaying adjuvant therapies and flaps are a better option in these patients. [44, 45] Temporalis muscle flap was the most common pedicled flap used in our review. Free flaps provide the bulk for reconstruction in larger defects and flexibility regarding the better cosmetic outcome.

Many complications can occur in orbital exenteration i.e. orbito-nasal or orbito-sinus fistulas, cerebrospinal fluid (CSF) leaks, dural exposure, and meningitis and flaps related complications like flap loss, sepsis, etc. [46] In our review many studies had Sino-orbital fistula and CSF leak. Orbital exenteration being a major procedure is justified only when required. Kuo et al. in his series concluded that the disease-specific survival was 97% at 1 year and 92% at 5 years. They also concluded that although it is an aggressive procedure, it is not an unreasonable procedure for well-selected patients. [47] Surgeons in the present systematic review also reported similar survival data.

Conclusion

We understand that Orbital exenteration is an extensive procedure and it has its indications. The aggressive pathology that requires orbital exenteration worldwide is mostly periorbital skin, sinus, and intraocular malignancies. The rising trend of these malignancies is a matter of concern and therapeutic nihilism should be avoided. The morbidity of the procedure is high with many surgical complications. However, in properly selected patients it can give better outcomes and survival.

Funding

None.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.