DR.KARTHIKEYAN MAHALINGAM

Dr. VINEY GUPTA, Dr.Shikha Gupta, Dr.KISHAN AZMIRA

Semi Finals

Abstract

The intraocular pressure (IOP) rise in thyroid associated ophthalmopathy (TAO) is often refractory to therapy. We report the management and prospective evaluation of 36 eyes of 18 TAO patients with raised IOP. Only 17 eyes (47.2%) responded to glaucoma medications, trabeculoplasty or filtration surgery. Rest 19 eyes (52.8%) had no response or needed orbital decompression. IOP of 5 (out of 6) eyes in non responders group normalised after orbital decompression. Non responders group had significantly higher males and higher central corneal thickness. 10 eyes of 6 patients showed paradoxical association of IOP with glaucoma progression. 5 eyes had high IOP with no progression and 5 eyes progressed even after reducing IOP. This explains the role of difference between venous outflow pressure & IOP in maintaining optic nerve perfusion and the need to manage the raised intraorbital pressure along with IOP.

Full Text

Introduction:

Grave’s disease is an autoimmune disorder characterized by hyperthyroidism, thyroid associated ophthalmopathy (TAO) and dermatopathy wherein most patients are hyperthyroid.^[1,2] Patients with TAO present with eyelid erythrema, conjunctival injection, eyelid retraction associated with exophthalmos or eyelid fibrosis.^[2] Increased orbital volume and fibrosis of extraocular muscles (EOM) may lead to bilateral exophthalmos, exposure keratitis, restriction of EOM movements, diplopia and compressive optic neuropathy.^[3] These patients also have raised intraocular pressure (IOP), first documented by Wesseley in 1918.^[4] It may be due to glycosaminoglycans accumulation in trabecular meshwork, increased episcleral venous and orbital pressure, responsiveness to steroids administered for TAO and restrictive myopathy (gaze related).^[5,6] Thyroid dysfunction and its treatment can also cause changes in IOP.^[7–11] The various options for management of raised IOP in TAO includes topical glaucoma medications, laser trabeculoplasty, glaucoma filteration surgery and treatment of TAO with steroids or orbital decompression. This raised IOP has poor response to medications which increase the aqueous outflow.^[12] Some patients may even have a paradoxical progression of the disease with IOP lowering.^[13] Inspite of high IOP, TAO  patients have lesser  tendency to glaucoma progression compared to general population.^[14] Maintaining optic nerve perfusion plays a major role in glaucoma progression. There is no standardized protocol for managing raised IOP in TAO. Most patients coming to glaucoma services are being treated like routine glaucoma patients without knowing the fact that decreasing IOP can also paradoxically; lead to glaucoma progression.^[13] There is a  paucity of  studies in literature which assess the effect of orbital decompression on IOP in patients with TAO. We aim to assess the course of raised IOP in TAO patients i.e, response to routine glaucoma treatment, orbital decompression and also its association with glaucoma progression.

Methods:

An ambispective observational study was conducted at the tertiarty eye care centre in North India after obtaining institutes ethical committee clearance. TAO Patients visiting glaucoma services and fullfilling our criteria were recruited after obtaining consent.

Inclusion criteria: Patients with thyroid associated ophthalmopathy defined by^[14] Otherwise unexplained eyelid retraction with lagophthalmos with or without other clinical signs of inflammation and with or without evidence of thyroid dysfunction (or) unexplained proptosis (Hertel ≥17 mm/ 2 mm interocular difference), extraocular muscle enlargement, orbital congestion, or inflammation accompanied by either eyelid retraction with lagophthalmos or evidence of thyroid dysfunction and untreated IOP > 21 mmHg in two or more occasions measured by goldmann applanation tonometry in primary gaze.

Exclusion criteria: Patients with other forms of glaucoma like primary open or closed angle glaucoma, traumatic glaucoma, uveitic glaucoma etc. Patient not willing to give consent or follow up.

Parameters like age, sex, IOP, duration of follow up, proptosis, central corneal thickness, cup-disc ratio (CDR), type of treatment given and thyroid status were  noted. Their past records were  noted and patients were  followed up prospectively. Data entry was done in Microsoft excel and SPSS version 23 was used for statistical analysis. The normal distribution of data was tested by the Kolmogorov-Smirnov test. Accordingly, continuous variables were reported with their mean ± standard deviation (SD) or median, interquartile range (IQR). Eyes were divided in to groups depending upon the response to glaucoma management and variables were compared. Pearson Chi square test was used for categorical variable. Since both the eyes of the patient were taken for analysis, generalized estimating equation (GEE) method was used to correct the bias.^[15] A P-value of <0.05 was considered significant.

Results:

42 eyes of 21 TAO pateints with OHT were studied. The mean age of participants was 43.8 ± 11.7 years with similar sex ratio (male: female::1:1). Median duration of follow up was 30 months (IQR: 18 to 37). Baseline IOP was 28.1 ± 6.4 mmHg, baseline CDR was 0.48 ± 0.16 : 1, CCT was 553.6 ± 31 mm, baseline Hertel’s measurement was 23.6 ± 3.9 mm.  IOP of 15 eyes (35.7%) (9 patients) normalised with topical glaucoma medications. These eyes were labelled as responders. 23 eyes (13 patients) where IOP was either not controlled or required orbital decompression for IOP control were termed as non-responders. 4 eyes with with IOP < 25 mmHg and no glaucomatous cupping or field defects were observed without glaucoma medications.  The characteristics of responders and non-responders are compared in Table 1. Six out of eight eyes (75%) which had undergone orbital decompression acheived IOP control. Three eyes underwent trabeculectomy with mitomycinC (MMC) out of which 2 needed orbital decompression. Two eyes underwent selective laser trabeculoplasty (SLT). Trabeculectomy and SLT were not helpul in IOP control. 20 eyes (47.6%) of eyes had paradoxical corellation of IOP with glaucoma progression. Out of these 20 eyes, in 6 eyes glaucoma progressed despite controlled IOP and 14 eyes did not show progression with high IOP over a median follow up of 36 months (IQR 24 to 40).

Table 1:

Characteristics	Responders (15 eyes)	Non-responders (23 eyes)	P value
Age (years)	44.5 ± 12.7	41.7 ± 9.8	0.54*
Sex (Male: Female)	1:2	2.8:1	0.02#
Thyroid status: Hyperthyroid Euthyroid Hypothyroid	6 (40%) 5 (33.3%) 4 (26.7%)	14 (60.9%) 1 (4.3%) 8 (34.8%)	0.05#
Baseline IOP (mmHg)	24.5 ± 5.1	30.8 ± 6.3	0.01*
Baseline CDR	0.42 ± 0.1 :1	0.53 ± 0.1 : 1	0.76*
CCT (mm)	544.7 ± 21	560.8 ± 34	0.12*
Proptosis	9 (60%)	20 (87%)	0.006*

^* Adjusted for presence of clustering by using Generalized Estimating Equation method,

^# Pearson Chi square test 

Discussion:

In our study, only one third of the eyes showed response to topical glaucoma medications. Majority of eyes had non-significant IOP reduction with multiple glaucoma medications, SLT or trabeculectomy with MMC. These non-responders showed significant male predominance and had significantly higher baseline IOP. Most of the non-responders were in either hyperthyroid or hypothyroid state. There are reports in literature suggesting that hypothyroidism can increase the IOP and treatment of hypothyroidism has been associated with control the IOP.^[10,11] Presence of proptosis was significantly higher in non-responders.

According to Cockerham et al, the prevalence of raised IOP in TAO patients was 24%, which was very high compared to general population (approximately 5%).^[14,16] The progression of ocular hypertension to glaucoma was less than 2% in TAO patients. This was less compared to general population with ocular hypertension which had 6.7% to 17.4% progression rate over 5 years (3.5% per year).^[17,18] In our study 14 eyes with raised IOP did not show progression of glaucoma. The plausible reasoning for this could be simultaneous increase in intraorbital pressure, which helps maintain optic nerve head perfusion.

In our study, 6 eyes showed glaucoma progression despite achieving target IOP. An indirect estimator of intraorbital pressure is venous outflow pressure (VOP).^[13] It is believed that VOP must be <5mmHg higher than IOP in order to maintain ocular perfusion pressure whereas a difference above that, can cause compromised perfusion leading to development of scotomas despite an actual lowering of IOP.^[13] Thus ophthalmodynamometry for assessment of VOP is helpful in patients who show signs of glaucomatous progression. Even if IOP is high but the difference with VOP is <5mmHg, IOP may not require lowering despite the high values seen.

Since the primary pathology in TAO, is raised intraorbital pressure, raised IOP is often refractory to medical management or glaucoma filtration surgeries. In our study, 75% of eyes (6 out of 8) eyes achieved target IOP after orbital decompression. In a study by Kalmann et al orbital decompression was performed in 5 TAO eyes with raised IOP and IOP was reduced in all eyes post-operatively.^[5]  Onaran et al showed that combined orbital bone and fat decompression in 72 eyes with TAO significantly decreased IOP and increased the superior ophthalmic vein blood flow velocity.^[19] Thus addressing the elevated episcleral venous pressure by orbital decompression would be helpful in reducing the IOP in patients with TAO.^[5,13,19]

Conclusion:

Risk factors for poor response to glaucoma therapy in TAO patients include male gender, higher baseline IOP, uncontrolled thyroid state and proptosis. If indicated, orbital decompression should be considered before planning for any glaucoma surgery. Maintaining the optic disc perfusion by keeping the balance between intraorbital pressure/VOP and IOP is required rather than reducing IOP in all cases. As measurement of VOP is not practically possible in all cases, stringent IOP reduction should not be considered unless glaucoma progression occurs (figure).

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