Congenital Glaucoma

Congenital Glaucoma is one of the most common causes of irreversible childhood blindness. This presentation covers this topic in detail that can aid physicians in effective patient care.
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1. CONGENITAL GLAUCOMA Presented By: Dr. Sahil Thakur Consultant Incharge: Dr. Suresh Kumar

2. Seminar SCHEME Terminology Classification Systems Epidemiology and Genetics Pathogenesis Clinical Presentation Diagnostic Examination EUA Medical Management Surgical Management Visual Rehabilitation Impact of Childhood Glaucoma Conclusion

3. According to age of onset CONGENITAL GLAUCOMA: Glaucoma exists at birth and usually before birth INFANTILE GLAUCOMA: Birth till 3 years of age JUVENILE GLAUCOMA: After the age of 3 years This terminology lacks clear cut demarcation so use is discouraged TERMINOLOGY

4. CHILDHOOD GLAUCOMAS Rare vision threatening heterogeneous group of diseases According to Shield’s classification of Childhood Glaucoma PRIMARY GLAUCOMA SECONDARY GLAUCOMA Congenital OAG Traumatic glaucoma Juvenile open angle glaucoma Secondary to intraocular neoplasm Associated with ocular abnormalities Secondary to uveitis Associated with systemic abnormalities Lens induced glaucoma After surgery for congenital cataract

5. PRIMARY: Due to maldevelopment of aqueous outflow system SECONDARY: Damage to aqueous outflow system due to maldevelopment of some other portion of eye DEVELOPMENTAL GLAUCOMA

6. Peripheral Mid peripheral Central Corneal size Anterior stromal defects Anomalous iris vessels Structural anomalies Flat iris insertion Concave iris insertion Does not include glaucoma in absence of developmental anomaly HALLMARK OF PRIMARY CONGENITAL GLAUCOMA HOSKIN CLASSIFICATION

7. ISOLATED TRABECULODYSGENESIS It is associated with primary congenital or developmental glaucoma IRIDO TRABECULODYSGENESIS Anterior stromal defect Hypoplasia of iris stroma Malformation of iris collarette Absence or marked reduction of crypt layer Common anomaly seen in Axenfield’s and Rieger’s anomaly Hyperplasia of iris stroma Diffuse thickening of iris

8. Anomalous iris vessels Persistence of tunica vasculosa lentis Anomalous superficial vessel Structural anomalies Holes, Aniridia and Colobomata CORNEO IRIDO TRABECULODYSGENESIS Peripheral corneal lesions extend no more than 2mm into clear cornea e.g. Posterior embryotoxon ( Axenfeld’s anomaly ) Mid peripheral or central opacities with thinning of stroma Microcornea : Rubella , PHPV , Nanophthalmos , Rieger’s anomaly Megalocornea: Axenfeld’s syndrome

9. PRIMARY CHILDHOOD GLAUCOMAS SECONDARY CHILDHOOD GLAUCOMAS IA Primary congenital glaucoma IB Juvenile open angle glaucoma IIA Glaucoma associated with non acquired ocular anomalies IIB Glaucoma associated with systemic disease or syndrome IIC Glaucoma associated with acquired condition IID Glaucoma following congenital cataract surgery Classification developed by members of CGRN and vetted by consensus committee of WGA in July 2013 CGRN CLASSIFICATION

10. PRIMARY Childhood GLAUCOMAS IA PRIMARY CONGENITAL GLAUCOMA Isolated angle anomalies Meets glaucoma definition Spontaneously arrested cases but with typical signs of PCG IB JUVENILE OPEN ANGLE GLAUCOMA No ocular enlargement No associated ocular anomalies /syndromes Open angle Meets glaucoma definition

11. SECONDARY CHILDHOOD GLAUCOMA Axenfeld’s Reiger anomaly Peter’s anomaly Ectropion uveae Congenital Iris Hypoplasia Aniridia Oculodermal melanocytosis Posterior Polymorphous Dystrophy Microphthalmos Microcornea Ectopia lentis IIA Conditions with predominantly ocular anomalies present at birth may or may not be associated with systemic signs

12. IIB Conditions predominantly with known syndromes systemic anomalies or systemic disease present at birth which may be associated with ocular signs Chromosomal disorders Connective Tissue Disorders Marfan’s Syndrome, Weil Marchesani’s Syndrome and Stickler’s Syndrome Metabolic disorders Homocysteinuria , Lowe’s Syndrome and Mucopolysaccharidosis Phacomatosis Neurofibromatosis, Sturge Weber and Klippel Trenuanay Weber Syndrome Congenital Rubella SECONDARY CHILDHOOD GLAUCOMA

13. IIC Glaucoma associated with acquired conditions which are not inherited or present at birth but develop after birth Uveitis Trauma Steroid induced Tumors Retinopathy of Prematurity SECONDARY CHILDHOOD GLAUCOMA

14. IOP> 21 mm of Hg plus at least one of the following: Optic disc cupping Progressive increase in VCDR Cup disc asymmetry of 0.2 or more Focal rim thinning Corneal findings Haab’s striae Diameter ≥11 mm in new born Diameter > 12 mm in < 1 yr old child Diameter > 13 mm any age Ocular enlargement like Progressive myopia / increasing axial length Visual field defect consistent with glaucomatous optic neuropathy with no observable reason for defect CGRN DEFINITION OF GLAUCOMA

15. Eyes meeting the CGRN glaucoma definition criteria are subcategorized into three groups on the basis of age: Neonatal: 0-1 month Infantile: 1 -24 months Late onset or late recognized: > 2 years DEFINITION OF GLAUCOMA SUSPECT Any 1 of the following IOP> 21 mm of H g on two separate occasions Suspicious optic disc appearance for glaucoma Increased CDR Increased corneal diameter or axial length in setting of normal IOP Supicious visual field defect for glaucoma

16. INCIDENCE Congenital glaucoma is responsible for between 4% and 18% of childhood blindness. In developed countries incidence is 1 in 10000 births 1 in 1250 in Slovakia Ophthalmologica . 1972;181:61–73 1 in 3300 in Andhra Pradesh Arch Ophthalmol . 1998;116:545–6 In t he Toronto experience, a review of 306 children diagnosed with childhood glaucoma, congenital glaucoma 38% followed by aphakic glaucoma 20% and Sturge –Weber syndrome-associated glaucoma 10%. J AAPOS 1999; 3: 308-15. In Dallas study 23% of patients had primary glaucoma, 45% had secondary glaucoma, and 31% were glaucoma suspects. Clinic Ophthalmol .2013; 7:1739-46 EPIDEMIOLOGY AND GENETICS

17. GENETICS Sporadic Familial patterns show recessive inheritance with variable degree of penetrance and multi factorial inheritance Increased incidence with high consanguinity Arch Ophthalmol 1998;116(4):545–546 LOCUS LOCATION INHERITANCE GENE GLC3A 2p21 AR CYP1B1 GLC3B 1p36 AR ? GLC3C 14q24.3 AR ? Genomics 1995;30:170-177 IOVS 2002; 43: 3015 GENETIC LOCI FOR PRIMARY CONGENITAL GLAUCOMA

18. Although spectrum of mutations in CYP1B1 have been implicated in PCG Very few reported genotype phenotype correlations Frameshift and R 390C are associated with severe phenotypes and poor prognosis IOVS April 2004 ;45 :1149-56

19. PATHOGENESIS

20. TM Ciliary muscle 5 months :Iris meets endothelium TM & ciliary muscle overlapping Allen et al :Arch Ophthalmol 53:783 1955 Cleavage of mesodermal tissue Normal development of the angle

21. Uveal tract splitting by cleavage or atrophy ciliary muscle is seen extending into iris Differential growth rate leading to slippage of ciliary muscle and ciliary body posteriorly

22. Typically bilateral but significant IOP elevation in one eye can occur in 25- 30 % of cases Commonly between 3-9 months Rarely at birth or up to 3 years of age CLINICAL PRESENTATION SIGNS AND SYMPTOMS

23. Site Signs Cornea Megalocornea Breaks in Descemet’s membrane Haab’s Striae Sclera Increased axial length Myopia Astigmatism Optic Nerve Cupping IOP Increased OCULAR EXPANSION

24. Cornea Megalocornea Corneal clouding Breaks in Descemet’s membrane Haab’s Striae Horizontal or curvilinear striae formed as endothelial cells lay down new basement membrane and hyaline ridges develop OCULAR EXPANSION

25. Sclera Scleral thinning Blue sclera Increased Axial length Myopia Astigmatism

26. Lens Stretching and rupture of zonules can cause lens subluxation Optic nerve cupping Rapid and early Reversible with normalization of pressure

27. To confirm the diagnosis of glaucoma Determining the type of glaucoma if present DIAGNOSTIC EXAMINATION Initial Evaluation Adnexal source of irritation Lacrimal system obstruction Visual response Corneal edema Opacification Preliminary digital tonometry

28. IOP evaluation can be done in sleepy infant or during bottle feeding using: Perkin’s Applanation Tonometer Tonopen 5-6 yr old child: GAT evaluation can be done

29. Refraction and Perimetry Myopia Astigmatism Visual Fields yield valuable information in older children Anterior Segment Evaluation Using portable slit lamp UBM: to detect any associated anterior segment anomalies Posterior Segment Evaluation With direct or indirect ophthalmoscope if there is no corneal clouding or o pacification B scan USG

30. EVALUATION UNDER ANAESTHEISA Sequence For EUA Corneal D iameter Tonometry Anterior Segment Evaluation Gonioscopy Fundus Refraction Pachymetry Axial Length Measurement To avoid unnecessary anesthesia ophthalmologist undertaking EUA should be able to perform surgery if indicated

31. Haab’s striae Corneal edema Corneal opacification: 80% of patients Posterior embryotoxon Megalocornea Measurement of Corneal D iameter: Hold the calipers on first appearance of white scleral fibers on one side and same point on other side. Accurate measurement using plastic gauge with calibrated holes. Can J Ophthalmology 1985; 20:93–97. CORNEAL FINDINGS

32. Age Normal Megalocornea Term 9.5 -10.5 11.5 1 yr 10-11.5 12-12.5 2yr 11-12 >12.5 Older child <12 >13 Sherwin Isenberg Formula in preterm babies C orneal Diameter=0.0014 * wt in gm + 6.3

33. Normal IOP varies with age: Mean IOP up to 12 year of age is12.2 +/-0.74 mm of Hg Mean IOP < 1 year of age is 8 +/- 2.5 mm of Hg J Pediatr Ophthalmol & Strabismus 2006; 43: 14 Tonometers Perkin’s hand held Applanation Tonometer Tonopen Schiotz Tonometer should be avoided Sources Of Error Effect of anesthesia Corneal surface distortion , edema Mackay Marg Tonometer is accurate IOP MEASUREMENT

34. ANAESTHETIC AGENTS AFFECT IOP Only raised IOP in EUA should never be the basis of diagnosis and treatment

35. Portable Slit Lamp Corneal findings Anterior chamber depth Anatomy of iris

36. Direct gonioscopy using Koeppe’s type direct goniolens with hand held slit lamp or microscope: Anterior insertion of iris with altered translucency of angle Lister’s morning mist: fine fluffy tissue covering peripheral iris Lochness Monster Phenomenon: loop of vessels of major arterial circle can be seen above iris Can visualize fundus through the same lens (in undilated pupil and with corneal edema ) GONIOSCOPY

37. Type 1 Type II The Glaucomas, Sampolesi , Springer, 2013

38. Possible if corneal edema or opacity do not hinder evaluation Avoid dilation if surgery is contemplated Direct ophthalmoscope Koeppe’s lens can be used with direct ophthalmoscope in small pupil Careful drawings and fundus photographs (using hand held fundus camera ) OPTIC NERVE HEAD EVALUATION

39. A scan measures axial length , anterior chamber depth , lens thickness Baseline value for comparative purpose B scan for posterior segment if opaque media precludes the view Can be used to visualize retinal or choroidal detachment/ mass lesion / etc. Ultrasonography

40. PARAMETER NORMAL MILD MODERATE SEVERE Corneal Diameter (mm) upto10.5 >10.5-12 >12-13 >13 IOP (mm of Hg) 11.5 11-20 >10-30 >30 Cup Disc ratio 0.3-0.4 >0.4-0.6 >0.6-0.8 >0.8 Last BCVA 20/20 <20/20-20/60 <20/60 – 20/200 <20/400- no PL Panicker et al IOVS 2004;45 :1149-56 SEVERITY INDEX

41. DIFFERENTIAL DIAGNOSIS BASED ON SYMPTOMS Epiphora and red eye Conjunctivitis Nasolacrimal duct obstruction Corneal epithelial defect Keratitis Anterior segment inflammation Conditions associated with corneal edema or opacification Birth trauma Congenital malformation Corneal dystrophy Keratitis Mucopolysaccharidosis Idiopathic

42. Conditions showing corneal enlargement Myopia Conditions showing actual or pseudo optic nerve cupping Physiologically large optic nerve cup Coloboma Atrophic optic nerve Hypoplastic optic nerve Malformation

43. MANAGEMENT SEQUENCE

44. SUPPORTIVE ROLE Preoperative :clear cornea for angle surgery Adjunctive modality: in combination with surgery if IOP is too high Temporary measure if infant is unfit for surgery ISSUE OF DRUG SAFETY IN CHILDREN S maller plasma volumes I mmature blood brain barrier I ncreased receptor sensitivity I ncreased systemic absorption MEDICAL TREATMENT

45. MEDICATIONS INDICATION CONTRAINDICATION B BLOCKERS Non selective- ( timolol -0.1 ,0.25 ,0.5 %) Selective (for reactive airways )- betaxolol 1 st line 2 nd line for older children Avoid in children with reactive airways , cardiac disease Side effects: bronchospasm bradycardia CAI (Oral acetazolamide -5-15mg/kg suspension ) Dorzolamide 2% Brinzolamide 1% 1 st line / 2 nd line – young children Avoid in children with corneal transplant Prostaglandins Latanoprost 0.005% Bimatoprost 0.03% Travoprost 0.004% 2 nd / 3 rd line Trichomegaly Redness Preoperative use – risk of inflammation Latanoprost use licensed in Europe since 2010 based on PANDA results

46. MEDICATION INDICATION CONTRAINDICATION Miotics Diarrhoea Interaction with succinylcholine for GA Headache , proinflammatory Adrenergic agonist Epinephrine Apraclonidine Brimonidine Not used Short term use in infants and after corneal transplant Only in older children 3 rd line or last resort Lack of efficacy DO NOT USE IN INFANTS / SMALL CHILDREN Lipophilic drugs –CNS side effects fatigue , somnolence

47. Definitive therapy in most cases Western world Early presentation with mild corneal edema at referral Goniotomy is the treatment of choice In India / Middle east Late presentation Goniotomy is not possible Trabeculotomy or combined trabeculectomy and trabeculotomy SURGICAL MANAGEMENT

48. Introduced By Barkan OBJECTIVE : Remove the obstructing tissue that causes resistance to aqueous outflow LENS: Swan J acob lens KNIFE: Barraquer knife Worst knife Swan spade Long needle Reported results show success rate of 80 %  J AAPOS.2001;5:281–4 GONIOTOMY

49. Pre-op Preparation Adequate miosis Facilitates retraction of iris from angle Steps After placing the goniotomy lens over cornea Anterior chamber is entered through a clear corneal incision (e.g. nasal goniotomy – temporal incision is given ) Knife is advanced towards the opposite angle parallel to iris and away from pupil and the angle is engaged by the blade tip which is swept circumferentially incising the nasal angle over 100-110 degree. Falling back of peripheral iris is the end point of surgery

50. Failure Failure of obtaining adequate incision during surgery Presence of peripheral anterior synechiae Fibrous proliferation Success rate of 70 – 93 % in large series after multiple goniotomies Ophthalmology 2011;118:236-40

51. TRABECULOTOMY AB EXTERNO Independently described by two surgeons in 1960 Burian : Trabeculotomy ab externo Smith: N ylon filament Trabeculotomy Beck and Lynch: 360 degree trabeculotomy using 6-0 polypropylene Recent: Illuminated Microcathether Principle : To cannulate S chlemm’s canal from external approach and then tear through TM into anterior chamber

52. GONIOTOMY VS TRABECULOTOMY Goniotomy Trabeculotomy Simple faster procedure Can be done in edematous or scarred cornea Does not disturb conjunctiva Does not require introduction of sharp instruments in anterior chamber Can be repeated one or more times Does not require adaptation to gonioprism Can be converted to trabeculectomy

53. COMBINED TRABECULOTOMY AND TRABECULECTOMY with /without MMC Trabeculectomy combined with trabeculotomy to increase the long term success Primary CTT : single operative procedure with better control of IOP in some populations e.g. India Trabeculotomy vs Trabeculectomy vs Combined procedure Favourable outcome with combined procedure but after 2 years advantage was not statistically significant Br J Ophthalmol 1999;83:317–322 . Mandal et al Primary CTT without MMC in299 eyes of 157 patients reported a success rate of 63.1 % by the end of 1 year Ophthalmology 2004; 111:283–290

54. Intraoperative use of mitomycin C has somewhat enhanced the success of procedure but with significant risk of complications Complications with MMC use in children Thin walled avascular bleb : risk of endophthalmitis Bleb leaks Wound rupture One reported series of retrospective comparison of trabeculectomy with or without MMC noted no significant difference in outcome J Glaucoma 2004;13:228–232

55. REGULAR FOLLOW UP For IOP monitoring Retinoscopy Amblyopia Therapy Optical Keratoplasty

56. SURGICAL SUCCESS Corneal clarity Decreased IOP Pale blebs Reversal or non progression of disc cupping Reversal or non progression of myopia Good visual recovery Surgical success has been defined as IOP <16 under GA or IOP < 21 mm of Hg with no progression of cupping or corneal diameter Qualified success: Maintenance of above pressures with single drug

57. Total of 148 eyes (85 patients) Trabeculotomy, trabeculectomy, or combined trabeculotomy-trabeculectomy (CTT) were compared: equal success rate Overall success rate was 80.4% One surgery 105 (70.9%), 34 eyes (23.0%) 2 surgeries, and 7 eyes (4.7%) had 3 surgeries A progressive decline in success rate over time was evident, as success rate dropped from 96.6% at 5 months to less than 50% after 11 years of follow-up  Surgical outcome of PCG better in infants presenting before 6 months Adjuvant topical anti glaucoma medications augment success rate

58. MANAGEMENT OF REFRACTORY GLAUCOMA / FAILED SURGERY UNFAVOURABLE FACTORS IN PEDIATRIC GLAUCOMA Low scleral rigidity Rapid healing process Exuberant scarring process Enlargement of glaucomatous eyes with thinning and distortion of intraocular anatomy

59. TRABECULECTOMY with or without MMC Indication Failed Angle S urgery Secondary G laucomas Success Rate Variable results in literature

60. Non Valved Molteno Baerveldt Valved AGV Indications Failed filtration surgery Failure to control IOP with medication post surgery Aphakic glaucoma Neovascular glaucoma GLAUCOMA DRAINAGE DEVICES

61. Aqueous Shunts AGV vs. Baerveldt vs MMC trabeculectomy in children <2 yrs: Retrospective study; Better IOP control with the GDDs than the MMC trabeculectomy group Cumulative success rates of 87% versus 36%, respectively, at 1year and even a larger difference of 53% versus 19% at 6 years. Am J Ophthalmol 2004;137 (6): 1163–1164 AGV vs MMC trabeculectomy in pediatric aphakic glaucoma: Prospective, randomized study Higher qualified success in the AGV(67%) vs the MMC trabeculectomy group (40%) Complication rates higher in the MMC trabeculectomy (40%) than AGV(26.7%)(differences were not statistically significant). Saudi Journal of Ophthalmology, 2011; 25:317–27

62. CYCLODESTRUCTIVE PROCEDURES Indications Failed angle surgery with minimal visual potential Failed trabeculectomy / GDD with poor central vision Anatomy precludes intraocular glaucoma surgery Options Trans-scleral cycloablation (Diode laser ) Endoscopic diode laser cycloablation Cyclocryotherapy

63. 21 year follow up 53 eyes included Mean logMAR VA was 0.61 ± 0.57. Good VA in 51%, Moderate VA in 30%, and Poor VA in 19% Deprivation Amblyopia (64%) was main cause of visual impairment with VA <20/50

64. VISUAL REHABILITATION Appropriate spectacle correction If problem persists for distance vision even telescopes can be prescribed Appropriate training for recommended device is must

65. VISUAL REHABILITATION Retrospective study of B/L congenital glaucoma 100 children , mean age 6.3 yrs (1 month-16 years) Success rate of early treatment is 70 to 80% Only 35% of all patients will have visual acuity better than 20/50, and 2% to 15% will remain blind. Regarding the optical prescriptions, 80% were corrected for myopia and 20% were for hyperopia and astigmatism. Optical devices for distance were prescribed for 34 % of the patients. All of the optical aids for distance were telescopic manual systems for one eye only Optical aids for near vision were necessary for 6% of the patients, and the most commonly prescribed were illuminated stand magnifiers of + 38 aspheric diopters Clinics 2009;64(8):725-30

66. Consider repeat trab , Drainage implant, Cyclodestruction . Goniotomy/Trabeculectomy/Combined Trab-Trab Surgical Outcome ? EUA after 3 weeks IOP controlled Evaluation after 3 months Normal IOP Evaluation after 3 months FU every 3 months Record IOP, CDR, VA Axial length, VF (if possible) IOP not controlled Add medical therapy If IOP not controlled repeat Trab-Trab Controlled VISUAL REHABILITATION U ncontrolled Very poor prognosis BROAD MANAGEMENT OUTLINE

67. IMPACT OF CHILDHOOD GLAUCOMA 119 children in the study, all grades of glaucoma Older children reported less impairment on CVAQC 1 , IVI-C 2 , and PedsQL 3 than younger children. Parents reported greater impact on their child's HR QoL than children reported themselves. Children with glaucoma report HR QoL scores similar to those described by children with severe congenital cardiac defects, who have undergone liver transplants, or who have acute lymphoblastic leukemia . (1) functional visual ability (FVA) with the Cardiff Visual Ability Questionnaire for Children (CVAQC), (2) VR QoL with the Impact of Vision Impairment for Children (IVI-C), and (3) HR QoL with the Paediatric Quality of Life Inventory ( PedsQL ) version 4.0.

68. PROGNOSIS OF CHILDHOOD GLAUCOMA 230 patients with 10 year follow up 79 having ocular hypertension with open angles or primary angle closure (PAC), 35 primary open angle glaucoma (POAG), 50 PAC glaucoma (PACG), 20 primary congenital glaucoma (PCG), 46 secondary glaucoma patients. 15% of primary congenital glaucomas (PCGs) showed a glaucomatous VF defect after 10 years. This study provides evidence that routine delivery of care can provide well controlled IOP in glaucomas, both primary and secondary, and the VF stabilized in about 90% of patients over a period of 10 years, with the currently available glaucoma medications and trabeculectomy.

69. INDIAN PRACTICE PATTERNS

70. Conclusion Congenital Glaucoma is a potentially treatable cause of irreversible childhood blindness provided it is picked up early. CGRN classification should be done for each case. EUA is the best method to clinically evaluate the patient. IOP should be taken immediately after induction with Tonopen or Perkin’s Tonometer to counter effect of anesthetic drugs. Management is mostly surgical. Goniotomy in West and Trab with augumented Trab forms the mainstay in our setup. Post operative life long follow up is vital. Amblyopia should always be treated to improve the QOL of the patient.