Causes of eye removal – analysis of 586 eyes

Background/Aim. Eye enucleation is one of the oldest surgical procedures. The aim of the study was to determine the causes of enucleation as seen in a major reference eye center in Serbia. Methods. Retrospective case series involving a review of all enucleation procedures performed in the period between January 2000 and December 2008 at the Institute for Eye Diseases, Clinical Center of Serbia, Belgrade. The collected information included the basic demographic data and diagnosis of the affected eye. The diagnosis was made based on history, clinical and histological examinations. Clinical indications for enucleation were categorized as tumors, glaucoma, trauma, infections and other diseases. A statistical analysis was made using the Student's t-test. Results. There were 586 patients, 315 male and 271 female in our series. The mean age was 57.81, ranging from 3 months to 96 years. The most common cause of enucleations was tumor (76.11%), (p < 0.05). Choroid melanoma was the most common etiology leading to enucleation (81.18%), followed by retinoblastoma (12.34%). A total of 8.02% of enucleations were performed due to glaucoma that was primarily neovascular in 42.55% of cases or caused by trauma in 38.8% of cases. Trauma was the third common etiology of enucleation, and it was acute in 56.26% of cases or resulted in phthisis bulbi in 31.25% of cases. Enucleation caused by inflammation was performed in 2.90% of cases, out of which 52.94% of enucleations occurred after perforation of the cornea. In the group of other diseases the most common cause of enucleation was atrophy of the eye ball. Conclusion. Neoplasm, neovascular glaucoma, acute eye injury and atrophy of the eye ball are the most common causes of enucleation.


Introduction
Enucleation is the removal of the eyeball, excluding the conjunctiva and the muscles.It is one of the oldest surgical procedures of the eye.Enucleation is performed in tertiary ophthalmological institutions when all treatment options are exhausted.Various eye diseases may lead to a blind and pain-ful eye or phthisis bulbi, the diseases that are the most common causes of enucleation.The indications for enucleation are the same worldwide [1][2][3][4][5][6][7][8] .Differences between some regions depend on the development of their respective health protection systems.There are numerous studies about the changing patterns of diseases leading to enucleation [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] .According to these studies, the following are the causes of enucleation: neoplasm, Strana 27 end-stage glaucoma, blunt or penetrating injuries of the eyeball, endophthalmitis, chronic uveitis, congenital glaucoma, etc.In developed countries, the most common causes of enucleation are ocular tumors, while in poor countries traumas of the eye are the most common etiology leading to enucleation.The introduction of new procedures in treatment of ocular tumors has significantly reduced the number of enucleations performed due to malignant choroidal melanoma 24 .One of the causes of enucleation is neovascular glaucoma.Panretinal photocoagulation and ligation of anterior ciliary arteries have significantly reduced the number of enucleations caused by neovascular glaucoma 25 .Endophthalmitis results in enucleation when other treatment options are exhausted.In the past few years serious intraocular infections led more often to evisceration than enucleation.The indications for enucleation and evisceration decreased in the last decade, most probably due to improved modalities of treatment 26 .Endophthalmitis after ulcerations and melting of the cornea may result in enucleation or evisceration 27 .
The aim of this study was to determine the causes of enucleation as seen in the major reference eye center in Serbia.

Methods
This case series involved a review of patients hospitalized during the period between January 2000 and December 2008 at the Institute for Eye Diseases, Clinical Center of Serbia (CCS), Belgrade, Serbia.Histories of the disease and pathohystological findings of the enucleated eyes were used as the data source.The patients were divided into age groups, subdivided into groups encompassing 10 years, those who were less than 10-year old, and patients who were more than 90-year-old.The distribution of enucleation was performed per age.The primary clinical indications for enucleation were categorized into five groups: tumors, glaucoma, trauma, inflammation and other.Tumors were classified as benign and malignant.Malignant tumors were divided into primary and metastasizing.Glaucoma was divided into the following groups: absolute, congenital, neovascular and posttraumatic.Traumas were divided into acute, fresh traumas and posttraumatic conditions, such as retinal ablation and massive hemorrhage.Inflammations of the eye resulting in enucleation were divided into: uveitis, keratitis with perforation, endophthalmitis, posttraumatic uveitis and other inflammatory conditions.Other diseases leading to enucleation were divided into old detachments, phthisis bulbi, congenital anomalies of the eye, atrophy of the eyeball and Coats' disease.
The statistical analysis was made by using the Student's t-test with statistical significance of p < 0.05.

Results
Enucleation was performed in 586 patients, 315 men and 271 women.The youngest patient was 3-month-old, while the oldest was 96-year-old.The average mean age of enucleated patients was 57.81 ± 7.50 years, and the age group most commonly affected by enucleation ranged between 50 and 70 years (Figure 1).

Fig. 1 -Age distribution of the patients with enucleated eyes
In the observed term the number of patients undergoing enucleation declined.In 70% of the patients, the difference in their respective age varied by 10%-15% (Figure 2).

Fig. 2 -Distribution of the performed enculeations per year in the observed term
The most common indication for enucleation was tumour (76.11%) as compared to other causes with the respective share ranging between 2.73% and 10.24%.Tumors are significantly the most common cause of enucleation, (p < 0.05).Glaucoma accounted for 8.02% of enucleation cases, trauma for 2.73%, inflammation for 2.90% of the cases, while other diseases and conditions resulted in enucleation in 10.24% of cases (Figure 3).The number of men and women affected by enucleation due to ocular tumour was approximately the same -228 men and 212 women, while enucleation caused by eye trauma occurred more often in men than women, i.e. 2/3 of male versus 1/3 of female patients.
Out of the total number of enucleations, enucleation was performed in 76.11% of the patients due to tumour.Benign tumors (choroidal hemangioma and leiomyomata) occurred with significantly lower probability of 1.3% as compared to malignant tumors that occurred in 98.7% of the cases, (p < 0.05).Primary malignant tumors accounted for 97.7% of all malignant tumors.Among primary malignant tumors, malignant choroidal melanoma was the most common cause of enucleation (81.18% of all malignant tumors).Malignant choroidal melanoma was significantly more common cause of enucleation in general (61.77%), as well as in the group of primary malignant tumors (81.18%).The probability of enucleation due to malignant choroidal melanoma did not vary a lot between the two genders (Table 1).
Glaucoma as a cause of enucleation accounted for 8.02% of the cases.Two third of patients suffering from glaucoma were men and 1/3 women.Absolute glaucoma occurred in 10.64% of the cases, congenital glaucoma in 8.51% of the cases, neovascular glaucoma in 42.55% of the cases and glaucoma resulting from trauma in 38.30% of the cases.Significantly, the most common cause of enucleation in case of glaucoma was neovascular glaucoma, followed by glaucoma caused by trauma (p < 0.05) (Table 2).
Trauma leading to enucleation occurred in 2.73% of all enucleation cases, having significantly higher incidence in men than women, (p < 0.05).In 56.26% of the cases there was an acute injury (p < 0.05).Esthetic reasons relating to phthisis bulbi caused enucleation in 31.25% of the cases, which was not significantly less than acute injuries resulting in enucleation (Table 3).Inflammation as the cause of enucleation occurred in 2.90% of all the enucleation cases.It was caused with a significant probability by keratitis leading to corneal perforation (52.94%) (p < 0.05), primarily in women.Other significant cause of enucleations resulting from inflammation was uveitis (23.53%), but it occurred with significantly lower incidence rate than keratitis with perforation.Other causes from the inflammation group such as endophthalmitis, exogenous postoperative uveitis and other inflammatory eye diseases were incidental events (Table 4).
Other diseases and conditions, such as: conditions after retinal detachment, phthisis bulbi, congenital anomalies of the eye, Coats' disease, atrophy of the eyeball and other diseases and conditions leading to enucleation occurred in 10.24% of all the enucleation cases.In the group of other diseases, a significant, most common cause of enucleation was the atrophy of eyeball (56.67%) (p < 0.05) (Table 5).

Discussion
In a tertiary ophthalmological institution -the Institute of Eye Diseases, CCS in Belgrade, during the period of 8 years enucleations were performed in 586 patients.The youngest patient was 3-month old, while the oldest was 96.The average mean age of the patients was 56.81 ± 7.50 years, as opposed to Gyasi et al. 22 where the mean age of 336 patients with enucleation was 36.4.The distribution of patients according to their respective age reveals that in 70% of patients the affected age differs by 10%-15%.The distribution of patients per year shows that the number of the performed enucleations has declined during the course of time, which may be explained by the progress made in the treatment of eye diseases that may lead to enucleation.
The most common indication for enucleation was tumour (76.11%).Other causes had a share of 2.73%-10.24%.Glaucoma caused enucleation in 8.02% of the cases, trauma in 2.73%, inflammation in 2.90% and other conditions in 10.24% of the cases.In comparing with the literature results, an increased number of enucleated eyes caused by malignant choroidal melanoma contrary to enucleations caused by retinoblastoma 24 can be explained by the fact that malignant tumors were diagnosed later, when the other methods of treatment could not be performed.Metastasizing tumors (2.3%) were diagnosed later because of secundary glaucoma.The ratio between men and women with the performed enucleation because of tumour was approximately the same (228 men and 212 women), while the number of enucleations due to trauma in men was higher than in women (2/3 men and 1/3 women).Contrary to our results, Gyasi et al. 22 revealed that the most often causes of enucleation were infections, in 47.9% of cases, followed by trauma, in 23.2% of cases, degenerations in 14.9% of cases, and other diseases in 8.9% of cases.Neoplasm was the fifth cause according to its incidence rate, i.e. 5.1%.Setlur et al. 23 in 2010 during a 60-yearfollow-up enucleations found that neoplasm was still the most common cause of enucleation, while there was a fluctuation with age in terms of an increased number of enucleations due to retinoblastoma as compared to malignant choroidal melanoma.In our study malignant tumors occurred in 98.7% of the cases.Among malignant tumors, the most often were malignant choroidal melanoma, in 81.18% of the cases, and retinoblastoma in 12.34% of the cases.The ratio between men and women was approximately the same (43.05%men and 38.13% women), contrary to retinoblastoma where men and women were equally represented.Glaucoma was the second most common cause of enucleation, accounting for 8.02% of the cases.A similar percentage, 8% of all enucleations, was observed during a 60-year-follow-up term by Setlur et al. 23 in 2010, where the number of enucleations Kneževi M, et al.Vojnosanit Pregl 2013; 70(1): 26-31.