WHEN DO WE CHOOSE SURGERY IN GLAUCOMA
PATIENT?
ANDIKA PRAHASTA
DEPARTMENT OF OPHTHALMOLOGY
PADJADJARAN UNIVERSITY / CICENDO EYE HOSPITAL
INTRODUCTION
• GLAUCOMA IS THE LEADING CAUSE OF IRREVERSIBLE BLINDNESS WORLDWIDE
• AFFECTING AN ESTIMATED 60 MILLION PEOPLE IN 2010
• THIS NUMBER IS EXPECTED TO INCREASE TO 80 MILLION IN 2020 BECAUSE OF BOTH DEMOGRAPHIC EXPANSION AND POPULATION AGING
• MORE THAN 50% OF SUFFERERS IN DEVELOPED COUNTRIES ARE UNAWARE OF THEIR CONDITION AND THIS FIGURE INCREASES TO OVER 90% IN THE DEVELOPING WORLD
Quigley HA, Broman AT: The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol 2006; 90: pp. 262-267.
Rein DB, Zhang P, Wirth KE, et. al.: The economic burden of major adult visual disorders in the United States. Arch Ophthalmol 2006; 124: pp. 1754-1760.
Resnikoff S, Pascolini D, Etaya’ale D, et al. Global data on visual impairment in the year 2002. Bull WHO. 2004;82:844-51.
Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90:262-7.
• GLAUCOMA RESULTS IN :
• VISUAL LOSS DUE TO A PROGRESSIVE LOSS OF RETINAL GANGLION CELLS (RGC)
• WITH CORRESPONDING VISUAL FIELD LOSS
• AND A CHARACTERISTIC ‘CUPPED’
APPEARANCE AT THE OPTIC NERVE HEAD.
VISUAL FIELD LOSS USUALLY BEGINS
PERIPHERALLY, BUT SOMETIMES AFFECTS
THE CENTRAL VISUAL FIELD FIRST
• THE ONLY MODIFIABLE RISK FACTOR FOR GLAUCOMA AT PRESENT IS THE
INTRAOCULAR PRESSURE (IOP)
• THE ONLY PROVEN METHOD TO DELAY OR PREVENT GLAUCOMATOUS OPTIC NEUROPATHY IS IOP LOWERING
• THIS MAY BE ACHIEVED BY MEDICATION,
LASER, OR SURGERY
ALWAYS
REMEMBER….
“Alphabet Soup” of RCTs
CNTGS
(Collaborative NTG Study)
EMGT
(Early Manifest Glaucoma Trial)
OHTS
(Ocular Hypertension Study)
CIGTS
(Collaborative Initial Glaucoma treatment Study)
AGIS
(Advanced Glaucoma Intervention Study) UKGTS
(UK Glaucoma Treatment Study)
Expands clinical knowledge
IOP reduction reduced the risk of progression Of OAG, including NTG
-Timolol reduced the risk of progression To glaucoma in eye with ocular hypertension -Thinner central corneas to be an independent
Risk factorfor progression to glaucoma
Initial surgery was more effective than medications in eye with advanced glaucoma
Latanoprost reduced the risk of progression in eye with
Open angle glaucoma, including NTG Important risk factors for glaucoma :
Higher IOP, exfoliation, older age, worst glaucoma status (MD value)
Sustained IOP reduction below 18 mmHg is Correlated with stability of visual fields - reducing IOP by 30% significantly reduces
the progression of the VF in NTG
EGS GUIDELINES
• ALL NEWLY DIAGNOSED GLAUCOMA PATIENTS SHOULD BE TESTED BY STANDARD AUTOMATED PERIMETRY THREE TIMES PER YEARS DURING THE FIRST TWO YEARS AFTER DIAGNOSIS
• RATE OF PROGRESSION CAN BE DETERMINDED EARLY
• RAPIDLY PROGRESSING EYES BE REVEALED WITH GREAT CERTAINTY
EGS 3rd guidelines
PURPOSE OF GLAUCOMA TREATMENT AND SURGERY
• THE OVERALL PURPOSE OF GLAUCOMA TREATMENT IS TO MAINTAIN VISUAL FUNCTION AND RELATED QUALITY OF LIFE AT A SUSTAINABLE COST
• GENERALLY, MEDICAL TREATMENT IS CONSIDERED FIRST, FOLLOWED BY LASER
• SURGERY IS CONSIDERED LATER BECAUSE MEDICAL TREATMENT IS SUFFICIENT TO CONTROL IOP IN MOST PATIENTS
• THE INCONVENIENCE OF LIFELONG EYE DROPS IS CONSIDERED A SMALLER IMPOSITION THAN RISKS OF SURGERY
• OFTEN MEDICAL TREATMENT IS THOUGHT TO BE ‘SUFFICIENT’
• MANY GLAUCOMA PATIENTS ARE MANAGED BY GENERAL OPHTHALMOLOGISTS WHO MAY NOT PERFORM GLAUCOMA SURGERY REGULARLY.
• THESE FACTORS ALL FAVOR LATER SURGERY.
MEDICAL VERSUS SURGICAL TREATMENT
• MEDICAL AND LASER TREATMENT ARE USUALLY THE FIRST LINES OF THERAPY
• THERE ARE SOME SITUATIONS WHERE EARLY SURGERY IS ADVISABLE
• SURGERY IS THE PRINCIPAL TREATMENT FOR :
• PRIMARY ANGLE CLOSURE (PERIPHERAL IRIDOTOMY/IRIDECTOMY, TO RELIEVE PUPIL BLOCK, LENS EXTRACTION)
• DEVELOPMENTAL GLAUCOMAS
• A NUMBER OF SECONDARY GLAUCOMAS :
• REMOVAL OF SUBLUXATED LENS IN SECONDARY ANGLE CLOSURE
• VITRECTOMY IN AQUEOUS MISDIRECTION
• REDUCING PAIN IN A POORLY SIGHTED EYE
• PROPER PATIENT SELECTION AND CHOICE OF THE MOST APPROPRIATE TECHNIQUE
• AS SURGERY ALWAYS INVOLVES SOME RISK, A CAREFUL ASSESSMENT OF RISK VERSUS THE POTENTIAL BENEFIT IS NEEDED; THIS AMOUNTS TO THE RISK OF NOT OPERATING
• THE FACTORS THAT DETERMINE THE LEVEL OF TREATMENT AGGRESSION DEPEND ON THE
SEVERITY OF DISEASE AT PRESENTATION (I.E. THE LOCATION AND EXTENT OF VISUAL FIELD)
• THE PATIENT'S LIFE EXPECTANCY
• THE DEGREE OF IOP ELEVATION
• THE TYPE OF GLAUCOMA
• UNILATERAL OR BILATERAL DISEASE
• THE FAMILY HISTORY
• A PREVIOUS HISTORY OF INTRAOCULAR OR CONJUNCTIVAL SURGERY
SURGERY?
MEDICAL VERSUS SURGICAL TREATMENT
• SURGERY IS RECOMMENDED FOR POAG IN THREE CIRCUMSTANCES :
1. ADVANCED VISUAL FIELD LOSS AT PRESENTATION, ESPECIALLY IN THE YOUNGER PATIENT. AGE AND STAGE OF DISEASE ARE
IMPORTANT RISK FACTORS FOR SEVERE VISUAL LOSS
2. FAILURE TO ACHIEVE A LEVEL OF IOP THAT WILL STABILIZE THE VISUAL FIELD ON TWO TO THREE TOPICAL MEDICATIONS
3. FAILURE TO TOLERATE OR ADHERE TO MEDICAL TREATMENT OR INABILITY TO USE MEDICAL TREATMENT
• PATIENTS PHYSICALLY UNABLE TO INSTILL EYE DROPS OR ABLE TO DO SO ONLY WITH DIFFICULTY
• WHERE LASER TRABECULOPLASTY IS EITHER INEFFECTIVE OR INSUFFICIENTLY EFFECTIVE
• POOR ADHERENCE AND INTOLERANCE OF MEDICAL THERAPY ARE BOTH COMMON PROBLEMS.
• IF THERE IS EVIDENCE OF PROGRESSION OF GLAUCOMA
RISK–BENEFIT ANALYSIS OF GLAUCOMA SURGERY
• GLAUCOMA TENDS TO BE A SLOWLY PROGRESSIVE DISEASE THAT CAN BE MONITORED OVER TIME VIA CHANGES IN OPTIC NERVE APPEARANCE, VISUAL FIELDS (VFS), AND OPTIC NERVE IMAGING.
• THE CONVENTIONAL APPROACH IS TO ATTEMPT MEDICAL THERAPY OR LASER TRABECULOPLASTY PRIOR TO SURGERY TO MINIMIZE RISK TO THE PATIENT.
• THE EFFICACY OF ANTIGLAUCOMA MEDICATIONS MAY BE LIMITED IN CERTAIN PATIENTS BY LOCAL AND SYSTEMIC SIDE EFFECTS.
• TRABECULECTOMY AND GLAUCOMA DRAINAGE DEVICE (GDD) IMPLANTATION, ARE ASSOCIATED WITH THE POTENTIAL FOR ADVERSE EFFECTS
• POSTOPERATIVE COMPLICATIONS FOLLOWING TRABECULECTOMY WITH ANTIMETABOLITE USE INCLUDE SHALLOW OR FLAT ANTERIOR CHAMBER, HYPOTONY, CHOROIDAL EFFUSIONS, BLEB ENCAPSULATION, BLEB LEAK, AND BLEBITIS/ENDOPHTHALMITIS.
• COMPLICATIONS RELATING MORE SPECIFICALLY TO GDD IMPLANTATION INCLUDE TUBE OBSTRUCTION, TUBE EROSION, AND MOTILITY DISTURBANCES
RISK–BENEFIT ANALYSIS OF GLAUCOMA SURGERY
Gedde SJ, Schiffman JC, Feuer WJ, et al., Tube versus Trabeculectomy Study Group. Treatment outcomes in the Tube Versus Trabeculectomy (TVT) study after five years of follow-up, Am J Ophthalmol, 2012;153:789–803.e2 Gedde SJ, Herndon LW, Brandt JD, et al., Tube Versus Trabeculectomy Study Group. Postoperative complications in the Tube Versus Trabeculectomy (TVT) study during five years of follow-up, Am J Ophthalmol, 2012;153:804–814.e1
WHAT FACTORS INFLUENCE MY DECISION-MAKING PROCESS?
• THE INTRAOCULAR PRESSURE (IOP) SHOULD FIRST BE EVALUATED AND ONE MUST TRY TO DETERMINE IF THE PATIENT IS PROGRESSING OR LIKELY TO PROGRESS AT THIS IOP.
• WHEN THE IOP IS AT A LEVEL THAT IS CLEARLY TOO HIGH, 30–50 MMHG, THEN THE DECISION IS STRAIGHTFORWARD.
• WHEN THE IOP IS IN THE 20–30 MMHG RANGE OR EVEN LOWER, THE DECISION IS NOT SO STRAIGHTFORWARD AND OTHER MEASURES NEED TO BE EVALUATED TO MAKE A PROPER DECISION.
• EVALUATE THE VFS AND SEE IF THERE IS CLEAR PROGRESSION ON TESTING.
• APPARENT PROGRESSION NECESSITATES CONFIRMATION WITH REPEAT VFS
• CHAUHAN ET AL. RECOMMEND A MINIMUM OF SIX VFS OVER 2 YEARS TO CONFIRM PROGRESSION
• COMPARE DISC PHOTOGRAPHS AND STRUCTURAL TESTING OF THE OPTIC NERVE TO SEE IF THERE HAS BEEN PROGRESSIVE DAMAGE. THIS IS MORE HELPFUL IS CASES OF PREPERIMETRIC GLAUCOMA AND ELEVATED IOP
• WHEN A PATIENT HAS ADVANCED DISEASE, WE FIND VF TESTING TO BE MORE HELPFUL IN JUDGING PROGRESSION.
Chauhan BC, Garway-Heath DF, Goñi FJ, et al., Practical recommendations for measuring rates of visual field change in glaucoma, Br J Ophthalmol, 2008;92:569–73.
WHAT FACTORS INFLUENCE MY DECISION-MAKING
PROCESS?
• PREVIOUS OCULAR SURGERY
• THE AGE OF THE PATIENT
• WE HAVE A LOWER THRESHOLD FOR SURGICAL INTERVENTION IN YOUNGER PATIENTS WITH ADVANCED DISEASE.
• FAMILY HISTORY IS AN ESTABLISHED RISK FACTOR FOR GLAUCOMA.
• ALWAYS INQUIRE ABOUT FIRST-DEGREE RELATIVES WITH THIS CONDITION AND SPECIFICALLY ASK ABOUT BLINDNESS IN THE FAMILY
WHAT FACTORS INFLUENCE MY DECISION-MAKING
PROCESS?
WHY IS IT SO DIFFICULT TO MAKE THE DECISION TO GO TO SURGERY?
• GLAUCOMA SURGERY IS NOT AS STRAIGHTFORWARD AS MANY OTHER PROCEDURES.
• EVEN WHEN SURGERY GOES WELL, THE POSTOPERATIVE PERIOD CAN BE FRAUGHT WITH COMPLICATIONS AND PATIENT COMPLAINTS.
• MULTIPLE PREOPERATIVE VISITS ARE NEEDED TO ESTABLISH A GOOD RAPPORT WITH THE PATIENT SO THAT THE FOLLOWING ISSUES CAN BE ADDRESSED:
• PATIENTS DO NOT SEE BETTER AND OFTEN SEE WORSE AFTER SURGERY (EXCEPT IF A COMBINED PROCEDURE IS PERFORMED)
• TRANSIENT VISION LOSS IS COMMON AFTER FILTERING SURGERY, AND VISUAL RECOVERY MAY TAKE UP TO 2 YEARS
• PATIENTS ARE OFTEN UNCOMFORTABLE AFTER SURGERY.
• THEIR EYES ARE RED AND IRRITATED
• PATIENTS DO NOT ALWAYS SEE OR UNDERSTAND THE NEED FOR SURGERY,GIVEN THE SLOW,ASYMPTOMATIC LOSS OF VISION THAT IS TYPICAL FOR GLAUCOMA
• THE RISKS FOR SURGERY
• HYPOTONY,SUPRACHOROIDAL HEMORRHAGE, BLEBITIS, ENDOPHTHALMITIS, DIPLOPIA, TUBE EROSION, AND CORNEAL DECOMPENSATION. MANY ARE VISION-THREATENING COMPLICATIONS THAT OFTEN NECESSITATE TRIPS BACK TO THE OPERATING ROOM.
WHY IS IT SO DIFFICULT TO MAKE THE DECISION TO GO TO SURGERY?
Francis BA, Hong B, Winarko J, et al., Vision loss and recovery after trabeculectomy: risk and associated factors, Arch Ophthalmol, 2011;129:1011–7
WHEN AND ON WHOM TO OPERATE?
• SURGERY IS THE MAINSTAY OF TREATMENT FOR A NUMBER OF TYPES OF GLAUCOMA INCLUDING PRIMARY ANGLE CLOSURE, SECONDARY, AND DEVELOPMENTAL GLAUCOMAS
• SURGERY IS INDICATED FOR POAG IN THE SITUATIONS DESCRIBED ABOVE, ESPECIALLY IN THOSE IN WHOM POAG IS ADVANCED AT THE TIME OF PRESENTATION, AND ESPECIALLY IF THE PATIENT IS YOUNGER.
• IT MIGHT BE WRONG TO DENY SURGERY TO THE BETTER EYE OF A VERY ELDERLY PATIENT WITH BORDERLINE IOP CONTROL IF THE FELLOW EYE HAS RECENTLY LOST VISION FROM GLAUCOMA
• SURGERY MAY BE OFFERED EARLIER IN THE DEVELOPING WORLD BECAUSE OF :
• LACK OF AVAILABILITY OR AFFORDABILITY OF MEDICATIONS
• LACK OF REGULAR LONG-TERM ACCESS TO MEDICAL CARE AS IN REMOTE COMMUNITIES
Francis BA, Hong B, Winarko J, et al., Vision loss and recovery after trabeculectomy: risk and associated factors, Arch Ophthalmol, 2011;129:1011–7
ON WHICH EYE TO OPERATE FIRST?
• THE EYE WITH THE HIGHER IOP AND THE FASTER PROGRESSING VISUAL FIELD
• IT IS NOT UNCOMMON IN ADVANCED GLAUCOMA TO OPERATE ON THE EYE WITH BETTER VISION IN ORDER TO PRESERVE CENTRAL VISION, RATHER THAN AN EYE IN WHICH FIXATION HAS ALREADY BEEN LOST.
• THE PATIENT MUST UNDERSTAND FULLY THE REASONS TO OPERATE ON THE BETTER EYE FIRST.
• IN DEVELOPING WORLD SITUATIONS, WHERE PATIENTS MAY FAIL TO UNDERSTAND THE REASONING AND PERMANENCE OF VISUAL LOSS IN THE WORSE EYE, AND THE RISK TO THE BETTER EYE.
• PATIENTS UNDERGOING SURGERY IN THE BETTER EYE MUST UNDERSTAND THE POTENTIAL FOR VISUAL BLURRING FOR SOME WEEKS AS THE EYE RECOVERS, AS WELL AS THE LONGER-TERM RISKS AND BENEFITS.
• IF SURGERY IS REQUIRED IN BOTH EYES, AND SURGERY TO THE MORE SEVERELY AFFECTED EYE HAS BEEN SUCCESSFUL, THE PATIENT MAY HAVE MORE CONFIDENCE AND BE BETTER PREPARED FOR SURGERY TO THE BETTER SIGHTED EYE.
• THIS RISK OF SURGERY HAS TO BE BALANCED AGAINST THE RISK OF VISUAL LOSS DUE TO GLAUCOMA IN AN ONLY EYE.
• METICULOUS SURGERY ERRING ON THE SIDE OF SAFETY IS ESSENTIAL.
ON WHICH EYE TO OPERATE FIRST?
SEEING THAT WE ACHIEVE GOOD OUTCOMES, SHOULD WE BE OPERATING EARLIER?
• PATIENTS WHO UNDERWENT TRABECULECTOMY HAD A MEAN IOP OF 14.5 MMHG AT 5 YEARS COMPARED WITH 18.5 MMHG FOR THOSE
PATIENTS TREATED WITH EITHER MEDICATION OR LASER THERAPY.
• THERE WAS A HIGHER RATE OF SUCCESS FOR THE SURGICAL GROUP THAT WAS SUSTAINED THROUGHOUT THE 5 YEARS OF FOLLOW-UP
• HE CIGTS STUDY FOUND THAT LOWERING IOP WITH INITIAL FILTERING SURGERY IS AS EFFECTIVE AS MEDICAL THERAPY FOR SLOWING
PROGRESSION OF VF LOSS.
• PATIENTS WITH MORE ADVANCED VF LOSS ACTUALLY DID BETTER WITH INITIAL SURGERY COMPARED WITH THOSE WHO WERE INITIALLY TREATED WITH MEDICATION
Migdal C, Gregory W, Hitchings R, Long-term functional outcome after early surgery compared with laser and medicine in open-angle glaucoma, Ophthalmology, 1994;101:1651–6; discussion 1657
• WILSON ET AL. CONDUCTED THE FIRST PROSPECTIVE, RANDOMIZED TRIAL COMPARING GDD WITH TRABECULECTOMY.
• A TOTAL OF 123 PATIENTS WERE RANDOMIZED TO RECEIVE AN AHMED GLAUCOMA VALVE OR TRABECULECTOMY AS A PRIMARY SURGICAL PROCEDURE FOR GLAUCOMA.
• WITH AN AVERAGE FOLLOW-UP OF 31 MONTHS, THE MEAN IOPS AND ADJUNCTIVE MEDICATIONS WERE SIMILAR IN THE TWO GROUPS.
• NO STATISTICALLY SIGNIFICANT DIFFERENCES BETWEEN GROUPS WERE FOUND IN VISUAL ACUITY, VF, AND SHORT- OR LONG-TERM COMPLICATIONS.
• THE CUMULATIVE PROBABILITIES OF SUCCESS WERE SIMILAR BETWEEN BOTH PROCEDURES (68.1 % TRABECULECTOMY GROUP VERSUS 69.8 % AHMED GROUP)
Wilson MR, Mendis U, Paliwal A, Haynatzka V, Long-term follow-up of primary glaucoma surgery with Ahmed glaucoma valve implant versus trabeculectomy, Am J Ophthalmol, 2003;136:464–70.
• THE TUBE VERSUS TRABECULECTOMY (TVT) STUDY WAS A MULTICENTER RANDOMIZED CLINICAL TRIAL THAT
EVALUATED THE SAFETY AND EFFICACY OF THE 350 MM2 BAERVELDT GLAUCOMA IMPLANT TO TRABECULECTOMY WITH MITOMYCIN-C IN PATIENTS WHO HAD UNDERGONE PREVIOUS CATARACT EXTRACTION WITH INTRAOCULAR LENS IMPLANTATION AND/OR FAILED FILTERING SURGERY.
• TUBE SHUNT SURGERY HAD A HIGHER SUCCESS RATE THAN TRABECULECTOMY THROUGHOUT 5 YEARS OF FOLLOW- UP (70.2 % TUBE GROUP VERSUS 53.1 %
TRABECULECTOMY GROUP).
Gedde SJ, Schiffman JC, Feuer WJ, et al., Tube versus Trabeculectomy Study Group. Treatment outcomes in the Tube Versus Trabeculectomy (TVT) study after five years of follow-up, Am J Ophthalmol, 2012;153:789–803.e2.
Gedde SJ, Herndon LW, Brandt JD, et al., Tube Versus Trabeculectomy Study Group. Postoperative complications in the Tube Versus Trabeculectomy (TVT) study during five years of follow-up, Am J Ophthalmol, 2012;153:804–814.e1
• A SURVEY OF THE MEMBERS OF THE AMERICAN GLAUCOMA SOCIETY WAS PERFORMED
• THOSE SURVEYED WERE ASKED TO ANSWER WHETHER THEY AGREE OR DISAGREE WITH THE FOLLOWING STATEMENT:
• “I AM MORE LIKELY TO PERFORM SURGERY AS INITIAL TREATMENT FOR PATIENTS WITH MODERATE TO SEVERE GLAUCOMA.”
• ONLY 20 % OF THOSE SURVEYED AGREED WITH THIS STATEMENT DESPITE THE RESULTS OF THE CIGTS STUDY, INDICATING THAT ALTHOUGH THERE IS GOOD EVIDENCE TO OPERATE EARLY
• MOST ELECT TO START WITH A MORE CONSERVATIVE APPROACH
SEEING THAT WE ACHIEVE GOOD OUTCOMES, SHOULD WE BE OPERATING EARLIER?
Migdal C, Gregory W, Hitchings R, Long-term functional outcome after early surgery compared with laser and medicine in open-angle glaucoma, Ophthalmology, 1994;101:1651–6; discussion 1657
Musch DC, Gillespie BW, Lichter PR, et al.; CIGTS Study Investigators. Visual field progression in the Collaborative Initial Glaucoma Treatment Study the impact of treatment and other baseline factors, Ophthalmology, 2009;116:200–7.
Panarelli JF, Banitt MR, Sidoti PA, et al., Clinical impact of 8 prospective, randomized, multicenter glaucoma trials, J Glaucoma, 2015;24:64–8
MEDICAL OR SURGICAL IN DEVELOPING WORLD?
• MEDICATION IS OFTEN UNAFFORDABLE, AND SURGERY MAY BE INDICATED AS AN OPPORTUNITY TO PREVENT PROGRESSION WITH ONE INTERVENTION ALONE.
• THE BARRIER TO TREATMENT OF GLAUCOMA IN THE DEVELOPING WORLD IS OFTEN LACK OF AWARENESS OR UNDERSTANDING OF THE NATURE OF THE CONDITION OR THAT PREVENTIVE TREATMENT IS IMPORTANT.
• FEW OPTION FOR TREATMENT EVEN WHEN IT IS AVAILABLE OR AFFORDABLE.
SUMMARY
• ASK FOUR QUESTIONS WHEN DECIDING TO PERFORM INCISIONAL GLAUCOMA SURGERY:
• 1. IS THE PATIENT PROGRESSING OR LIKELY TO PROGRESS AT THE CURRENT IOP?
2. WHAT IS THE RATE OF PROGRESSION?
3. HOW OLD IS THE PATIENT, AND WILL HE OR SHE LOSE USEFUL VISION IN HIS OR HER LIFE TIME?
4. DO THE POTENTIAL BENEFITS OF SURGERY OUTWEIGH THE RISKS?
• THE DECISION OF WHEN TO PERFORM INCISIONAL GLAUCOMA SURGERY WILL RELY ON THE EXPERIENCE OF THE SURGEON, AND A COMBINATION OF OBJECTIVE AND SUBJECTIVE
FACTORS UNIQUE TO EACH PATIENT
