Ismail K Jalili

FRCS, DO, FRCOphth

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15

Aetiological Classifications

I K Jalili
15.1   Introduction

15.2   Demographical Aspects (subregional Variations)

 
15.3   Aetiological groups  
15.4  Hereditary condition
15.5   Non-hereditary conditions

15.1

Introduction

In this study, among the total number of  669 patients, the aetiologies of the causative condition were as follows: (Figure 15.1)

1.      Hereditary: This is the largest aetiological group comprising a total of 519 patients, 243 pedigrees and 310 sibships. (77.6%)

2.      Non-Hereditary Conditions: This group comprises 90 patients and sibships with 89 pedigrees. (13.4%)

3.     Aetiology Undetermined:  This includes 60 patients with the same number of pedigrees and sibships. (9%)

      The aetiological classification of cases by region is shown in Tables 15.1 and by gender in Table Table 15.2.

     
Figure 15.1 Aetiological classification of conditions in the survey on childhood onset visual impairment in the West Bank and Gaza Strip
     
Table 15.1  Distribution of cases by aetiology and region

 

West Bank

Gaza Strip

Others

Total

Hereditary

<16

163

76.2

141

86.0

6

22.2

310

76.4

16+

102

76.7

103

82.4

4

66.7

209

79.5

Subtotal

265

76.4

244

84.4

10

33.3

519

77.6

Non-Hereditary

<16

26

12.1

9

5.5

5

18.5

40

9.9

16+

29

21.8

20

16.0

1

16.7

50

19.0

Subtotal

55

15.9

29

10.0

6

66.6

90

13.5

Undetermined

<16

25

0.9

14

1.2

16

3.7

55

1.2

16+

2

1.5

2

1.6

1

16.7

5

1.9

Subtotal

27

7.8

16

5.5

17

51.5

60

9.0

Grand Total

All age groups

347

289

33

669

Total 16

214

164

27

405

Total 16+

133

125

6

264

     

Table 15.2  Gender in hereditary and non-hereditary cases
 

 

West Bank

Gaza Strip

Total

 

No.

M:F

No.

M:F

No.

M:F

 

Hereditary

 

 

 

 

 

 

 

All series   M

127

0.9

146

1.5

277

1.1

 

F

138

 

98

242

 

Subtotal

265

 

244

 

519

 

 

School      M

78

0.95

73

1.3

152

1.1

 

Children     F

82

55

140

 

Non-Hereditary

 

 

All Series    M

25

0.9

19

1.9

49

1.2

 

F

30

10

41

 

Subtotal

55

 

29

 

90

 

 

School      M

21

2

9

4.5

32

2.5

 

Children     F

10

2

13

 

TOTAL

347

 

289

 

669

 

 

     
Table 15.3  Distribution of both hereditary and non-hereditary cases in West Bank’s sub-regions

 

North

Centre

South

U/D

Total

Non-hereditary

18

32.7

20

36.4

12

21.8

5

9.1

55

100

Hereditary

85

32.1

124

46.8

39

14.7

17

6.4

265

100

Total

103

32.2

144

45.0

51

15.9

22

6.9

320

100

% Non-Hereditary

17.5

13.9

23.5

22.7

17.2


Percentages in bold italic  U/D: Undetermined region

15.2  Demography of Aetiological Groups (Sub regional variations)
Regional Variation
 

In the West Bank, the percentages of both the hereditary and non-hereditary conditions in the northern regions (Jenin, Qalqilya, Tul-Karem and Nablus) are equal. There is preponderance of hereditary conditions in the central regions (Ramalla, Jerusalem, and Bethlehem) and of the non-hereditary conditions in the southern regions of Hebron. (Table 15.4)

There are wide variations in the proportions of hereditary and non-hereditary conditions accor­ding to the type of locality (i.e urban, rural or camps).  Over 50% of both the hereditary and the non-hereditary cases live in villages.

Table 15.4  Distribution of aetiological cohorts by type of dwelling

 

Villages

Towns

Camps

UD

Totals

West Bank

 

 

 

 

 

 

 

 

 

Non-hereditary

31

56.4

20

36.4

3

5.5

1

1.8

55

100

Hereditary

148

55.8

79

29.8

24

9.1

14

5.3

265

100

Subtotal

179

55.9

99

30.9

27

8.4

15

4.7

320

100

% non- hereditary

 

17.3

 

20.2

 

11

 

6.7

 

17

Gaza Strip 

Non-hereditary

6

20.7

7

24.1

15

52

1

3.4

29

100

Hereditary

73

29.9

95

38.9

66

27

10

4.1

244

100

Subtotal

79

28.9

102

37.4

81

30

11

4

273

100

% non-hereditary

 

7.6

 

6.9

 

19

 

9.1

 

11

Both regions*

 

 

 

 

 

 

 

 

 

 

All aetiologies

269

40.2

226

33.8

111

17

63

9.4

669

100

% non-hereditary

 

14.3

 

13.4

 

16.7

 

7.7

 

14.2

* Including others from undetermined regions.   Percentages in bold italic

     
15.3 Aetiological Groups

Undetermined Aetiology

In 60 patients it was not possible to ascertain the aetiology. (Table 15.5) The lack of available family information and pedigree charts in this group was an important factor in this shortfall; 55 of these patients were recruited from the out patients at St John Ophthalmic Hospital. Also, the lack of detailed information made it impossible to compile data on the marriage patterns and consanguinity. Conditions of undetermined aetiology formed 13.3% and 15.6% of the pedigree and sibships respectively. 

  The age groups in the undetermined cases are predominantly in the < 16 cohort (n=56) (9.6% of the total series). The M:F ratio is 2.3:1 in the West Bank and 2.5:1 in Gaza Strip. The ratio resembles that of the non-hereditary postnatal cases in the < 16 (Table 15.5). The regional distribution of patients in this group was; West Bank, 27; Gaza Strip, 16; undetermined from either regions 17.      

  In this group the main site of pathology was the lens in 66.6% (n=40) followed by the whole globe 18% (n=11). The main conditions diagnosed in this group were; congenital cataract (n=40); buphthalmos (n= 9); and others (n=11).

Table 15.5  Undetermined conditions

Possible genetic aetiology         50   (83.0%)
Possible non genetic aetiology     5   (8.3%)
         Prenatal factors   (1)
         Postnatal factors (4)
Either prenatal or genetic           2   (3.3%)
Postnatal or genetic                  1   (1.6%)
Undetermined                           2   (3.3%)

Total                                     60    100%

     
15.4 Hereditary Conditions

Hereditary Aetiology

Heredity formed the major bulk of cases in this survey. Of the 669 patients with bilateral visual disorders, 517 cases were hereditary in origin, that is 77.6%. Of these, 265 patients (51%) are in the West Bank and 244 (47%) in the Gaza Strip. A further 10 (2%) are patients whose families live in Israel or are from either the West Bank or the Gaza Strip but where the exact origin is uncertain. (Tables 15.3, 15.4)

  The M:F ratio for the West Bank hereditary series (n= 163) is identical to the sex ratio in the general population at 1:1 in the <16. In the 16+ cohort the ratio 0.79:1 (n=102). (Table 15.2) The latter ratio resulted from a female excess of 12 patients. In the Gaza Strip, the ratio in the <16 is 1.39:1 (n=141) and in the 16+, 1.64:1 (n=103). This is the result of an excess of 23 and 25 male patients in each cohort respectively. The overall ratio, however, in the total hereditary group is 1.14:1 combining the <16 at 1.17:1 and the 16+ at 1.1, similar to the ratio in the general population.

Hereditary lens disorders is the second commonest genetic group is lens disorders with 94 cases forming 18.1% of the total genetic cohort. This leaves 14 (9.6%) cases of non-hereditary aetiology and 37 (25.5%) cases of undetermined aetiology. (Table 15.6)

Excluding the latter, hereditary conditions form 87% of the lens cases. The hereditary group comprises primarily genetic congenital cataract with 81 patients (86%) followed by ectopia lentis with 13 patients (14%). An account of the clinical aspects of this group is found in chapter 17.

Table 15.6 Proportions of lens conditions and congenital cataract.
Age Total series

Hereditary

Non-Hereditary

Undetermined

All Lens categories

All ages

145

21.7

94

65

14

9.6

37

25.5

<16  

105

26

57

54.3

11

10.5

37

35

Cong. Cataract (including aphakia)

All ages

132

19.7

81

61.4

14

10.6

37

28

<16  

94

23.2

46

49

12

12.7

37

39.4

All Cataract (primary and secondary pathology)

All ages

153

22.8

100

63.4

15

9.8

38

34

<16  

111

27.4

61

55

13

11.7

38

34

     

Hereditary retinal conditions constituted 97% of the retina cases with the commonest conditions being retinal dystrophies, albinism and high myopia 4.8% (n=22).  (Tables 15.7 and 15.8)

In the Gaza Strip, this was as high as 99% of all the retinal conditions.  There is an obvious male preponderance in the Gaza Strip (ratio 1.5:1) with the reverse observed in the West Bank (ratio 0.7:1), averaging in both regions at 1:1.

 Other hereditary conditions included congenital glaucoma, small eyes (microphthalmos and anophthalmos, and congenital hereditary corneal oedema (chapter 17).

Table 15.7  Retinal dystrophies in the anatomical ‘retina’ category

 

West Bank

Gaza Strip

Total Series

 

M

F

Total

M/F

M

F

Total

M/F

M

F

Total a

M/F

All Retina

72

95

167

0.8:1

84

58

142

1.4:1

156

153

317

1:1

Genetic

68

92

160

0.7:1

83

57

140

1.5:1

151

149

306

1:1

% Genetic

94

97

96

 

99

98

99

 

97

97

97

 

 

     
Table 15.8 Pedigrees and sibships in the genetic retinal series

 

Pedigrees

Sibships

 

 

West Bank

Gaza Strip

Total

West Bank

Gaza Strip

Total

 

All Retina

96

91

44

42

147

100

113

60

68

36

188

100

Genetic

89

84

42

40

136

100

106

60

66

37

177

100

% Genetic

93

 

95

 

93

 

94

 

97

 

94

 

S'ship/Pedig a

1.18

 

1.55

 

1.28

 

-

 

-

 

-

-


Percentages bold italic a: ratio of sibships/pedigrees

 

     
15.5 Non-Hereditary Conditions


Number of cases
Of the 699 cases in the survey, the aetiology in 90 (3.3%) cases was acquired. Of those, 55 cases (61%) were from the West Bank forming and 29 (39%) from the Gaza Strip. This forms a ratio of 1.9:1 which is only slightly higher than the ratio of the population in the two regions. (15.1 to 15.4) 

Age
There is a preponderance of adults in this category with an <16 and 16+   ratio of 0.8:1. This is the reverse of the equivalent ratio in the hereditary condition which is 1.48:1.

Gender
The sex ratio in this group (1.19:1) is comparable to the ratio in hereditary conditions. Causes

Causations
The causation of the 90 cases of non-hereditary conditions span the whole spectrum of non-hereditary factors as follows (Figure 15.3): -

A)  Prenatal factors with 24 patients (27%). 
B)  Perinatal factors (including neonatal) with 10 patients (11%).
C)  Postnatal factors, the largest group with 55 patients (61.8%).
D)  Uncertain non-genetic, 1 patient.

Pathologies in Non-Hereditary Conditions

Whole globe pathologies formed the main group of conditions in the non-hereditary causes with 31 patients constituting 35% of cases. This is followed by corneal conditions comprising 16 cases (18%) and thirdly by optic nerve disorders with 14 cases (16%), whilst lens disorders had 11 cases (12%) and retinal conditions 9 cases (10%).

A breakdown of all non-hereditary cases are listed in Table A15.1. (Chapter 17 Appendix)

Table 15.9 Intrauterine causes
1. Intrauterine infections (IUI)
    a. Congenital Toxoplasmosis    3
    b. Congenital Rubella              1
    c. Undetermined type of IUI   10
2. Possible IUI                           5
3. Possible drug intake                3
4. Either IUI or drug intake          1
5. Undetermined IU Factors         1

                                    Total 24
     
Figure 15.3  Aetiological factors in non-hereditary conditions

     

Prenatal Factors  

Among the 24 cases of prenatal aetiologies, the majority are most probably secondary to intrauterine infection constituting 79% of the prenatal cases and making this factor the most important cause for prenatal conditions which amounts to 3.6% of the total series of 669. In most cases of the undetermined type of intra uterine infections, it was not possible to ascertain the exact cause although CMV virus infection is a likely possibility. There were 3 cases with possible drug intake in the first trimester (Table A15.1).

Visual Acuities

Visual acuities in the prenatal group of patients were severely compromised with 71% (n= 17) blind and nearly two thirds of the blind having NLP. The visual acuities in cases with lenticular aetiology varied between categories ‘2’ and ‘3’

Table 15.10 Visual acuities in prenatal conditions

Category ‘5’  (NLP)    10
Category ‘4’ (blind)     7
Category ‘3’ (SVI)      1
Category ‘2’  (VI)       3
Category ‘1’ (NVI)      1
Others                     2
              
                Total      24


Anatomical Sites

The lens was the main site of pathology and found in 50% of the prenatal cases, followed by the whole globe in 33%. The main clinical conditions in this subgroup are CC followed by microphthalmos. 

Demography

There is a significant preponderance of prenatal conditions in the West Bank versus Gaza Strip with a ratio of 15:1.
The contributory factors in the patients studied are enumerated in Table A15.1) 

Perinatal and Neonatal Causes

This is a very small group consisting of 10 patients only. Four of these patients were in the West Bank and three in the Gaza Strip. The number of females in the Gaza Strip was double that of males (2 and 1). Two thirds (n=4) of the perinatal problems were caused byretinopathy of prematurity and the other third (n=2) were from birth hypoxia. (Figure 15.4)

There were only 4 cases where the cause of blindness was due to factors occurring in the first month after birth. One was described as due to ophthalmia, two due to harmful topical medications (one of which was iatrogenic as a result of a medical error), and the fourth case was secondary to surgical complications in the first month (neither the nature of the condition nor of the surgery were clear). Anatomical sites of the pathologies were retina in 4; phthisis bulbi, 2; corneal pathology, 2; and optic atrophy, 1.  

Visual acuities were also severely affected in this category with 100% SVI/BL (NLP,5; BL, 3; SVI,1; and category ‘7’, 1).

Postnatal Factors

This is the largest group of the acquired non-genetic cases with 55 patients, forming 62% of the non-hereditary conditions and 8% of the total series. Twenty of these patients were under the age of 16 (36%) and 35 (64%) are adults. This group comprised 31 patients from the West Bank as opposed to 21 in the Gaza Strip, thus producing a ratio of 1.5:1, which was fairly similar to the population ratio, taking into account the small size of the sample and the possible presence of a few scattered cases in the West Bank that had not been examined (population ratio 1.78:1). There were an additional 2 where the origin was not determined and one from Israel.

  The M:F ratio in the various age cohorts in this group shows that with the exception of 16+ cohort in the West Bank, there is a male preponderance the highest being in the Gaza Strip <16 cohort at 4:1, followed by the West Bank <16 cohort at 2.3:1 and finally the Gaza Strip <16 cohort at 1.6:1. The West Bank 16+ cohort showed female preponderance with a ratio of 0.36:1.

  In this aetiological group, 40% of cases belonged to the whole globe (n=22), 25.5% to the cornea (n=14), 20% to the optic nerve (n=11) and 9% to the retina (n=5). The 14 corneal cases were of corneal scarring and 1 was staphyloma. Eleven of these were 16+ and 3 <16. In the whole globe cases, 12 were phthisical/atrophic eyes and in 3, eyes had been removed.

  Trauma accounted for 11 cases distributed between the West Bank (6) and the Gaza Strip (5) (West Bank/Gaza Strip ratio 1.2:1 compared to a population ratio of 1.78:1). M:F ratio was 1.2:1. Of these cases only 1 was from head injury and the rest were ocular including 4 from bomb explosion.

  Blindness ranked very high at 83% of the total with 60% having NLP (n=33). The figure reaches 87% when combining the blind with the SVI. 

Table A15.1 sums up all the conditions in the non-hereditary conditions.

     
Table A15.1  A breakdown of the non-hereditary condition encountered in the survey

 

Ismail K Jalili 2000-2016