Study of ophthalmic manifestations in tubercular meningitis patients

Introduction: Ophthalmic complications are very common in tuberculous meningitis (TBM) patients, understanding the ocular problems in tubercular meningitis patients is very important for ophthalmologists to intervene on time to prevent irreversible damage to eye. Hence this investigation has been undertaken to study ophthalmic manifestations in suspected tubercular meningitis patients in both Pediatric and adult population in Basaveshwara teaching and general hospital, Kalaburagi attached to Mahadevappa Rampure Medical College (MRMC). Materials and Mathods: The study was conducted at Basaveshwara Teaching and General Hospital, Kalaburagi attached to M.R. Medical College, from Dec 2011 to May 2013. 100 admitted patients diagnosed with TB meningitis, were selected for the study. The patients were divided into 2 groups. Group A consisted of TBM patients who were conscious and cooperative for ophthalmic examination. Group B consisted of TBM patients who were in a state of coma, uncooperative for ophthalmic evaluation. Results: Out of the 100 patients, 64% had ocular findings. In our study 22% had cranial nerve palsy. Fundus changes were seen in 50% of the patients. Around 22% patients had visual acuity, CSF protein content was considerably high in all patients. Hydrocephalous was seen in 31% (20) patients. Conclusion: In our study it was observed that most of TBM patients had ocular findings, CSF protein was found in many patients and after treatment there was improvement in ocular problems. We suggest further research with larger sample size to support our findings.


Introduction
Tuberculosis (TB) is still increasing in India at an alarming rate. The most serious form of tuberculosis is tubercular meningitis (TBM). 1 TBM causes many complications in both children and adult patients. The close association between optic nerve and meninges produces many ocular problems. Commonly found ophthalmic complications in TBM are Optic neuritis, optic atrophy, papilloedema. It may be associated with lid retraction, tonic deviation of eyes, and pupillary abnormality in size. Patients with high CSF protein content are prone for primary optic atropy. Choroidal tubercles and papilloedema are signs of grave complications. 2 Ophthalmic complications are very common in tuberculous meningitis patients, so understanding the ocular problems in tubercular meningitis patients is very important for ophthalmologists to intervene on time to prevent its irreversible damage to the eye.
Hence this study of ophthalmic manifestations in tubercular meningitis patients has been carried out to know the type of ophthalmic complications present in TBM patients.

Materials and Methods
The study was conducted at Basaveshwara Teaching and General Hospital, Kalaburagi attached to M.R. Medical College. The study period was from Dec 2011 to May 2013. 100 admitted patients referred from the Medicine, Pediatrics and Neurology department, diagnosed with TB meningitis, were selected for the study.
Out of 100 cases selected, 80 were in the adult age group and 20 were from Pediatric age. A meticulous history was taken from all the cases, followed by a thorough ocular examination.

Inclusion
Observations were made on the modes of presentation and a criterion was applied for diagnosis and the visual outcome in the individual patients. 2.5% 0r 10% for adults and children 1 drop 2.5%) every 3-5 minutes and tropicamide (1%) eye drops, posterior segment examination was done with direct ophthalmoscopy and also by binocular indirect ophthalmoscopy 5. Fundus examination with 78D and 90D Volk lenses was also done 6. Clinical findings were recorded in a proforma sheet 7. Patients were referred back to the medicine and pediatric department for further treatment.
Children below the age of three and those uncooperative for vision were tested depending upon whether they reacted to the light source and whether they followed the light source projected onto their eyes, thus confirming their 'PLPR' status (perception of light-PL; projection of rays-PR).
For patients where visual acuity couldn't be tested (unconscious/ventilated), outcome was based upon their pupillary reactions and their fundus findings.
A little older children and those co-operative for vision were tested by Snellens chart or were tested depending upon whether they followed the light/objects in front of them.
Their families were asked about the child's facial recognition, social smile and how he responded to objects at home.

Treatment of tubercular meningitis
All patients in the pediatric age group, diagnosed with TBM were given the following treatment. Prior to starting the treatment, following investigations were done-1. Complete blood count 2. Mantoux test 3. Chest x-ray 4. Lumbar puncture-TC, DC, Protein, Sugar, ADA, Chloride. 5. CT Brain 6. Liver Function Test (LFT).
After the intensive phase was completed three drug combinations consisting of HRZ was continued for a period of 7 months. 3. Tab Prednisolone-2 mg/ kg/day for 6 weeks followed by which the drug was tapered off in 2 weeks. 4. IV Mannitol -5 mi/kg was given for 3 days. 5. Tab pyridoxine -40 mg/ kg. 6. Anticonvulsants were given in case the child had seizures Eg-tab phenobarbitone (adults; 60-180mg daily at night. children; 2.5-4mg/kg once or twice daily).

Follow-up
The patient was reviewed after 15 days of discharge from the hospital and called in every month thereafter till the course of treatment was completed.
LFT was done after 15 days of starting on ATT drugs and repeated at 1 month follow-up.

Treatment regime in adults
After the routine investigations were done (as mentioned above) and the patient diagnosed as TBM, the following treatment was started: 1. Tab Forecoxconsisting of HRZE was given for 6 months in the dose of 2-0-0. H-300mgOD R-600rngOD Z-l.5 gOD E-1.5 mg/kg/day'. If the weight of the patient is < 30 kg Forecox-150 mg was prescribed. 2. IV Dexarnethasone 8mg/kg TID is started along with the ATT drugs. 3. Tab Eptoin-100 rng for 3 months for epilepsy.

Follow-up
Patients were called for a monthly follow up and then bi-rnonthly follow up till the symptoms subsided.

Statistical Analysis 1. Risk factors for development of oculo-visual anomalies
were compared with chi square test 2. Difference in proportions was tested by chi square test.

Results
A total of 100 admitted patients diagnosed with tubercular meningitis were taken up for this study.
The patients were divided into 2 groups. Group A consisted of TBM patients who were conscious and cooperative for ophthalmic examination.
Group B consisted of TBM patients who were in a state of coma, uncooperative for ophthalmic evaluation  Males constituted 51(51%) of the total cases while females constituted 49(49%). Majority i.e 55(55%) were in the age group between 15-40 years of age. 30(30%) were in the pediatric age group and 15(15%) were in the age group between 4 1-60 years. Mean age of males is 24.26±12.52 Mean age of females is 24.404±13.64As the p> 0.05, the difference in the age distribution of cases among males and females is not significant.  Cranial nerve palsy was seen in 22(22%) patients 1. It was observed that, out of the 22, maximum patients had VI Cranial Nerve Palsy 13% 2. Followed by the VI nerve was the involvement of III Cranial nerve of 6%. 3. VII nerve involvement was seen in only 1%. 4. Combined nerve involvement was seen in 6%. Combined nerve palsy was often seen in association with 2'nerve involvement (5out 6). II and VI nerve constituted 4 patients II and III nerve constituted 2 patients III and VI nerve involvement was seen in 1 patient.
The p value is more than 0.05 which shows that there is no significant difference in the cranial nerve palsies between males and females.  Fundus changes were seen in 50(50%) of the patients. Papilloederna was seen as the most common finding, in 21% of patients and Papillitis constituted 12%.
Blindness occurring secondary to optic atrophy. Optic atrophy occurred as post-papilloedema/papillits (secondary) or as primary optic atrophy. Optic atrophy was either complete (total pallor of disc) or incomplete (temporal pallor). 1. Optic atrophy in the form partial atrophy was 05(5%) 2. Total Optic atrophy was seen in 12(12%)  The above findings were in regards to the worse affected eye. Out of the 100, static perimetry was done only in patients with stage II and III. Out of the 64 patients, in 34 patients, perimetry was normal. 5 patients showed enlargement of blind spot.
6 patients showed peripheral constriction of the visual field.
3 patients showed central scotoma and 1 patient showed centrocecalscotoma.
In 15 patients, perimetry could not be recorded because they were in stage III, unco-operative/ unconscious state and those who showed complete optic atrophy, visual field testing is not possible. A lower level of glucose (<40) was seen in 80% of the cases, whereas only 3 cases had glucose >70mg/dl The mean value of glucose was 80% of the cases who had a cobweb appearance of CSF and protein was found to be elevated in all cases. 27 cases had >300 mg CSF protein, max being 2g. The mean value of protein was CSF cells were elevated in all cases All cases had >60% lymphocyte predominance. Tuberculorna was found in 1(1.51%) patient. Cerebral edema was seen in 2(3.03%).
CT scan was not done in 34 patients. Hydrocephalous 20 20 4 Interrupted treatment 1 1 The above table shows that more than half of the patients had ocular manifestations. i.e 64 out of 100 patients The protein content was considerably high in all patients Hydrocephalous was seen in 20 patients. It is clear that there is significant difference in the severity of risk factors between the groups with group B having a higher risk of ocular anomalies than group A and Group A2 a higher risk than Al.

Risk factor
S-Significant HS-Highly Significant VHS-Very Highly Significant NS-Not Significant. The above table shows that mortality rate and poor visual outcome is more amongst group B population. i.e Stage III of Tubercular Meningitis. Out of the 12 patients who presented in stage III, 5(41.66%) expired during their stay at the hospital and 7(58.33%) had oculovisual anomalies.

Discussion
In our study out of 100 TBM patients 64% had ocular manifestations, Verma et al, 3 investigated 50 cases of pediatric tubercular meningitis, they observed that 76% had ophthalmic problems. There was frequent involvement of third nerve and sixth cranial nerve. It's been observed that highest incidence of mortality was with sixth nerve palsy which is followed by a complete third canial nerve palsy.
In our study 22% had cranial nerve palsy in that 13% had 6 nerve palsy and 6% had 3 rd nerve palsy, Lamba PA et al carried out a study on 48 children with TBM, in which Optic disc changes (papillitis) constituted 62%, papillary involvement was in 48% of patients and cranial nerves (3 rd ) involvement was found in 28% of patients. 4 22% had visual acuity, 21% had papilloedema, 12% had papillitis Mishra M, et al, carried out study on 100 patients with T.B. meningitis, 82% of patients had ocular complications in which 40% presented with diminished visual acuity, 22% had papilloedema, 25% presented with ocular paresis, 18% had pale disc and 10% choroidal tubercles.; 22% had evidence of obstructive hydrocephalus diagnosed by ventriculogram/C.T, 20% cases had vasculitis diagnosed by angiography and 12% of patients had Tuberculoma. 5 In our findings 80% percent showed low level of CSF glucose, 27 cases had CSF protein more than 300mg and CT scan was done in 66 patients out of this 21(31%) had hydrocephalus, basal meningitis was seen in 15%, tuberculoma was observed in 1.5% and cerebral edema was found in 3% of patients. Sinha et al, conducted study on 101 patients of T.B. meningitis, in which at the study enrolment 74 patients had normal vision and 27 patients presented with low vision. During the process of study 13 patients died and remaining 88 patients who survived at 6 months, in 88 survived patients 68 patients had good vision, 11 patients presented with low vision and 9 patients had presented with blindness. Papilloedema, cranial nerve palsies, raised cerebrospinal fluid protein (> 1 g/L), and presence of optochiasmatic arachnoiditis in MRI diagnosis were predictors of vision deterioration. The predictors of blindness at 6 months were observed to be papilledema, vision acuity < 6/18, cranial nerve palsies, tuberculous meningitis stage II or III, raised cerebrospinal fluid protein (> 1 g/L), optochiasmatic arachnoiditis, and optochiasmal tuberculoma. 6 Benneggi A et al, found a case with severe ocular manifestations in a patient with tuberculous meningitis. 7 Anupriya A et al carried out a study on 163 patients and had observed that Optochiasmatic Arachnoiditis may occur as a complication of T.B. meningitis. 8 Smith et al, found that tuberculosis was mediating factor in acquired abducens nerve palsy in children. 9 In our investigation visual acuity improved from 1month post-operative period to 3 rd month post-operative period, fundus changes like papilloedema and papillitis became nil after 3 rd month post-operative period. Mortality rate and poor visual outcome was found more amongst stage III TBM patients. It is clear that there is significant difference in the severity of risk factors between the groups with group B having a higher risk of ocular anomalies than group A.
In our study it was observed that most of TBM patients had ocular findings. Timely intervention for TBM can prevent severity of ocular problems. We suggest further research with larger sample size to support our findings