I use Indesign, Illustrator, and Photoshop CS5 Middle Eastern to don't have much problem with Khmer Unicode.
If you use CS5 without Middle Eastern, try to research about Open Type function
Make sure you have
ចូលក្នុងប្រអប់ Character > Show Option > Open Type >
ជ្រើសយក៖
Standard Ligature
Contextual Alternates